bluuebunny/crossref_metadata_2025 huggingface dataset:
Susceptibility of Ocular Tissues to Autoimmune Diseases
Authors: KAMINSKI HENRY J. , LI ZHUYI , RICHMONDS CHELLIAH , RUFF ROBERT L. , KUSNER LINDA
Published: January 2004

Abstract: The orbital tissues may form a unique immunological environment, as evidenced by autoimmune disorders that specifically target orbital tissues, particularly myasthenia gravis (MG) and Graves' ophthalmopathy (GO). The reasons for the preferential susceptibility are likely to be multiple, based on the interplay of molecular and physiological properties of extraocular muscles (EOM), the unique requirements of the ocular motor system, and the specific autoimmune pathology. Of general importance, even a minor loss of EOM force generation will sufficiently misalign the visual axes to produce dramatic symptoms, and proprioceptive feedback is limited to overcome such a deficit. Particular to MG, EOM synapses appear susceptible to neuromuscular blockade, the autoimmune pathology differs between ocular and generalized MG patients, and the influence of complement regulatory factors may be less prominent in preventing damage at EOM neuromuscular junctions. GO pathogenesis is poorly understood, but shared epitopes of orbital fibroblasts, EOM, and thyroid could lead to specific autoimmune targeting of these tissues. The differential response of orbital fibroblasts to cytokines may be a key factor in disease development. Greater appreciation of the immunologic environment of orbital tissues may lead to therapies specifically designed for orbital autoimmune diseases.
Induction of Myasthenia Gravis in HLA Transgenic Mice by Immunization with Human Acetylcholine Receptors
Authors: YANG HUAN , GOLUSZKO ELZBIETA , DAVID CHELLA , OKITA DAVID K. , CONTI‐FINE BIANCA , CHAN TEH‐SHENG , POUSSIN MATHILDE A. , CHRISTADOSS PREMKUMAR
Published: January 2004

Abstract: We utilized HLA transgenic mice to identify the dominant epitopes on the human (H)‐AChR α subunit. The cytoplasmic H‐AChR peptide α320–337 was the dominant T cell epitope for DQ8, DR3, and DQ8×DQ6 F1 mice. The H‐AChR‐immunized HLA‐DQ8, DR3, DQ8×DR3 F1 and DQ8×DQ6 F1 mice developed clinical EAMG, whereas HLA‐DQ6 mice were less susceptible.
Myasthenia Gravis (MG): Epidemiological Data and Prognostic Factors
Authors: MANTEGAZZA RENATO , BAGGI FULVIO , ANTOZZI CARLO , CONFALONIERI PAOLO , MORANDI LUCIA , BERNASCONI PIA , ANDREETTA FRANCESCA , SIMONCINI ORNELLA , CAMPANELLA ANGELA , BEGHI ETTORE , CORNELIO FERDINANDO
Published: January 2004

Abstract:Data from 756 myasthenic patients were analyzed for diagnostic criteria, clinical aspects, and therapeutic approaches. The patients were followed up at our institution from 1981 to 2001. Clinical evaluation was performed according to the myasthenia gravis score adopted at our clinic. Clinical features of each patient (comprising demographic, clinical, neurophysiological, immunological, radiological, and surgical data, as well as serial myasthenia gravis scores) were filed in a relational database containing more than 7000 records. Clinical efficacy and variables influencing outcome were assessed by life‐table methods and Cox proportional hazards regression analysis. Complete stable remission, as defined by the Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America, was the end point for good prognosis. Four hundred and ninety‐nine patients (66%) were female and 257 (34%) were male. Mean follow‐up was 55.1 ± 48.1 months. Onset of symptoms peaked in the third decade in females, whereas the male distribution was bimodal with peaks in the third and sixth decades. Modality of myasthenia gravis presentation was as follows: ocular, 39.3%; generalized, 28.5%; bulbar, 31.3%; and respiratory, 0.8%. Thymectomy was carried out on 63.7% of our patients by different approaches: (1) transcervical; (2) transsternal; (3) video‐thoracoscopic mini‐invasive surgery. The last approach has been preferentially used in more recent years and accounted for 62.4% of the thymectomized myasthenia gravis population. Univariate analysis and Kaplan‐Meier analysis showed that variables such as sex (female), age at onset (below 40 years), thymectomy, and histological diagnosis of thymic hyperplasia were significantly associated with complete stable remission, whereas on multivariate analysis only age at onset below 40 years and thymectomy were confirmed.
Myasthenia Gravis in Individuals over 40
Authors: AARLI JOHAN A. , ROMI FREDRIK , SKEIE GEIR OLVE , GILHUS NILS ERIK
Published: January 2004

Abstract: Myasthenia gravis (MG) in individuals over 40 years of age comprises three groups: early‐onset MG with prolonged disease duration, late‐onset MG with thymoma, and late‐onset of nonthymomatous MG. The clinical features do not differ between the three groups, except that early‐onset patients with prolonged disease duration usually have a less severe disease. More than 60% of our MG patients are now more than 50 years of age, often with disease onset after age 40. Although 2 out of the 3 patients in Erb's original description had onset of myasthenic symptoms after age 40, this was apparently infrequent in 1879, when the disease was first identified. Onset of MG after age 40 is now common. For example, in our material, 88/184 (47.8%) had onset of MG after age 40. Eighteen (20.5%) had a thymoma. The female:male ratio in the early‐onset group was 2.4:1, whereas it was 1:1.1 among those with onset after age 40. There was no human leukocyte antigen association for MG with thymoma. Antibodies to the acetylcholine receptor were detected in 88% of sera from nonthymomatous MG and in 100% of those with late‐onset MG with thymoma. Antibodies to titin were found in sera from 85.7% of MG patients with thymoma (all age groups) and in 58% of nonthymomatous MG with late onset and acetylcholine receptor antibodies. Late‐onset, nonthymomatous MG comprises two subgroups, one corresponding to delayed early onset and one immunologically similar to that seen in patients with MG and thymoma.
Standards of Measurements in Myasthenia Gravis
Authors: GAJDOS P. , SHARSHAR T. , CHEVRET S.
Published: January 2004

Abstract: Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis. Several muscle scoring systems have been proposed for assessing muscle strength in such patients. The aim of the present study is to assess the validity and interobserver agreement of these muscle scores.
Three Forms of Immune Myasthenia
Authors: AGIUS MARK A. , RICHMAN DAVID P. , FAIRCLOUGH ROBERT H. , AARLI JOHAN , GILHUS NILS ERIK , ROMI FREDRIK
Published: January 2004

Abstract: We propose a new classification for immune myasthenia based on antibody pattern. The types of immune myasthenia presently characterized by known antibody targets segregate into three groups: type 1, in which the muscle target is the acetylcholine receptor only; type 2, in which titin antibodies are present in addition to acetylcholine receptor antibodies; and type 3, in which muscle‐specific kinase antibodies are present in the absence of acetylcholine receptor antibodies. The immune target is unknown in the patients with immune myasthenia not associated with these antibodies. This classification has advantages over the present classifications as regards homogeneity of groups, etiology, mechanism of disease, and prognosis.
Treatment Principles in the Management of Autoimmune Myasthenia Gravis
Authors: RICHMAN DAVID P. , AGIUS MARK A.
Published: January 2004

Abstract:The pathogenesis of myasthenia gravis (MG) involves a T cell‐directed antibody‐mediated autoimmune attack on the nicotinic acetylcholine receptor (AChR) or, occasionally, on other postsynaptic antigens. The antibodies induce their effects through complement‐mediated destruction of the postsynaptic endplate membrane with resultant reduction in endplate AChR, and to a lesser degree by increased turnover of endplate AChR or blockade of AChR function. Considerable progress in the treatment of MG has accrued from so‐called symptomatic treatments, including improved critical care of seriously ill patients and medications (e.g., cholinesterase inhibitors) increasing the concentration of acetylcholine at the remaining endplate AChRs. Information from other autoimmune diseases and from the response of the normal immune system to invading pathogens supports the view that the course of MG is characterized by exacerbations and remissions. Therefore, the goal in MG treatment is to induce and maintain a remission. This usually involves combinations of short‐term and long‐term immunosuppressive agents. Selection of the particular combinations of agents in a given patient is guided by the goal of minimizing the cost/benefit ratio of the regimen in an individual patient. In general, the plan involves an initial forceful attack followed by a slow and measured withdrawal.
Development of a Thymectomy Trial in Nonthymomatous Myasthenia Gravis Patients Receiving Immunosuppressive Therapy
Authors: WOLFE GIL I. , KAMINSKI HENRY J. , JARETZKI ALFRED , SWAN ANTHONY , NEWSOM‐DAVIS JOHN
Published: January 2004

Abstract: Thymectomy has been regularly used in the management of nonthymomatous autoimmune myasthenia gravis (MG), but its benefits have not been established in a randomized, controlled trial. The widespread use of thymectomy in MG patients without thymoma is largely based on retrospective, nonrandomized case series that have produced a consensus that the procedure is sometimes beneficial. Still, the benefits and utilization of thymectomy are actively debated among MG experts. In this paper, we describe the development of a multicenter, international trial to determine whether extended transsternal thymectomy reduces corticosteroid requirements for patients with generalized AChR antibody‐positive nonthymomatous MG.
Thymectomy and Antimuscle Antibodies in Nonthymomatous Myasthenia Gravis
Authors: ROMI FREDRIK , GILHUS NILS E. , VARHAUG JAN E. , MYKING ANDREAS , SKEIE GEIR O. , AARLI JOHAN A.
Published: January 2004

Abstract: The clinical effect of thymectomy in early‐ and late‐onset myasthenia gravis (MG) and the correlation to MG severity, pharmacological treatment, and antimuscle antibodies were examined in two series of consecutive acetylcholine receptor (AChR) antibody‐positive nonthymoma MG patients. The results indicate a benefit of thymectomy in early‐onset MG, but no obvious clinical benefit in late‐onset MG. The presence of muscle autoantibodies did not influence the outcome of thymectomy in early‐onset MG. In late‐onset MG, improvement is least likely in patients with titin and/or RyR antibodies. Thymectomy should always be considered shortly after MG onset in early‐onset MG patients and might only be considered in late‐onset patients who have early‐onset‐like immunological characteristics.
Mycophenolate Mofetil for Myasthenia Gravis A Double‐Blind, Placebo‐Controlled Pilot Study
Authors: MERIGGIOLI MATTHEW N. , ROWIN JULIE , RICHMAN JUDITH G. , LEURGANS SUE
Published: January 2004

Abstract: Mycophenolate mofetil (MM) is an immunosuppressive agent developed and originally used to prevent acute rejection of solid‐organ transplantation. There have been preliminary reports of its successful use in the treatment of autoimmune myasthenia gravis (MG). We conducted a double‐blind, placebo‐controlled pilot trial of MM in the treatment of suboptimally controlled, stable MG. Results of this pilot study are promising and suggestive of greater improvement in the patients who received MM compared to placebo.
Lambert‐Eaton Myasthenic Syndrome
Authors: SANDERS DONALD B.
Published: January 2004

Abstract: A high index of suspicion is essential in arriving at the correct diagnosis of Lambert‐Eaton myasthenic syndrome (LEMS). LEMS should be considered in the differential in any patient who has proximal weakness, reduced or absent muscle stretch reflexes, and dry mouth. Weakness predominates in hip and shoulder muscles, but may also affect ocular and oropharyngeal muscles to a lesser extent. The diagnosis is confirmed by demonstrating characteristic electromyographic findings—low‐amplitude muscle responses that increase dramatically after activation. Most patients also have circulating antibodies to the voltage‐gated calcium channel. Half the patients with LEMS have a malignancy, usually small‐cell lung cancer. The diagnosis should trigger an intensive search for malignancy, especially in older patients with a history of smoking. Younger, nonsmoking patients are likely to have LEMS as part of a more general autoimmune state. Successful treatment of the underlying cancer leads to improvement in many patients. More than 85% of patients have clinically significant benefit from 3,4‐diaminopyridine (DAP). In over half of these, the improvement is marked. If severe weakness persists despite DAP, immunotherapy should be considered. Plasma exchange and high‐dose immunoglobulin induce transient improvement in many patients, but function rarely becomes normal. Combinations of prednisone, azathioprine, or cyclosporine have been used with variable success. Improvement, if any, occurs only after many months and requires chronic administration of immunosuppressive medications at significant doses. The long‐term prognosis in LEMS is determined by the presence of cancer or other autoimmune disease.
Treatment of Autoimmune Disease by Adoptive Cellular Gene Therapy
Authors: TARNER INGO H. , SLAVIN ANTHONY J. , McBRIDE JACQUELINE , LEVICNIK ALENKA , SMITH RICHARD , NOLAN GARRY P. , CONTAG CHRISTOPHER H. , FATHMAN C. GARRISON
Published: January 2004

Abstract: Autoimmune disorders represent inappropriate immune responses directed at self‐tissue. Antigen‐specific CD4+ T cells and antigen‐presenting dendritic cells (DCs) are important mediators in the pathogenesis of auto‐immune disease and thus are ideal candidates for adoptive cellular gene therapy, an ex vivo approach to therapeutic gene transfer. Using retrovirally transduced cells and luciferase bioluminescence, we have demonstrated that primary T cells, T cell hybridomas, and DCs rapidly and preferentially home to the sites of inflammation in animal models of multiple sclerosis, arthritis, and diabetes. These cells, transduced with retroviral vectors to drive expression of various “regulatory proteins” such as IL‐4, IL‐10, IL‐12p40, and anti‐TNF scFv, deliver these immunoregulatory proteins to the inflamed lesions, providing therapy for experimental autoimmune encephalitis (EAE), collagen‐induced arthritis (CIA), and nonobese diabetic mice (NOD).
Specific Immunotherapy of Experimental Myasthenia by Genetically Engineered APCs
Authors: DRACHMAN D. B. , WU J‐M. , MIAGKOV A. , WILLIAMS M. A. , ADAMS R. N. , WU B.
Published: January 2004

Abstract:Although treatment of MG with general immunosuppressive agents is often effective, it has important drawbacks, including suppression of the immune system as a whole, with the risks of infection and neoplasia, and numerous other adverse side effects. Ideally, treatment of MG should eliminate the specific pathogenic autoimmune response to AChR, without otherwise suppressing the immune system or producing other adverse side effects. Although antibodies to AChR are directly responsible for the loss of AChRs at neuromuscular junctions in MG, the AChR antibody response is T cell‐dependent, and immunotherapy directed at T cells can abrogate the autoantibody response, with resulting benefit. As in other autoimmune diseases, the T cell response in MG is highly heterogeneous. The design of specific immunotherapy must take this heterogeneity into account and target the entire repertoire of AChR‐specific T cells. We describe our investigation of a novel strategy for specific immunotherapy of MG, involving gene transfer to convert antigen‐presenting cells (APCs) to “guided missiles” that target AChR‐specific T cells, and that induce apoptosis and elimination of those T cells. This strategy uses the ability of APCs from a given individual to present the entire spectrum of AChR epitopes unique for that individual, and thereby to target the entire repertoire of antigen‐specific T cells of the same individual. Using viral vectors, we have genetically engineered the APCs to process and present the most important domain of the AChR molecule, and to express a “warhead” of Fas ligand (FasL) to eliminate the activated AChR‐specific T cells with which they interact. Our results show that the APCs express the appropriate gene products, and effectively and specifically eliminate AChR‐specific T cells by the Fas/FasL pathway, while sparing T cells of other specificities.
Suppression of Myasthenia Gravis by Antigen‐Specific Mucosal Tolerance and Modulation of Cytokines and Costimulatory Factors
Authors: SOUROUJON MIRIAM C. , MAITI PRASANTA K. , FEFERMAN TALI , IM SIN‐HYEOG , RAVEH LILY , FUCHS SARA
Published: January 2004

Abstract: We have shown that mucosal administration of recombinant fragments corresponding to the human acetylcholine receptor (AChR) α subunit suppresses chronic ongoing experimental autoimmune myasthenia gravis (EAMG) in rats. Treated animals exhibit a Th1 to Th2/Th3 shift in their cytokine profile and downregulation of costimulatory factors. However, application of a xenogeneic recombinant fragment may have limitations when considered as a possible approach for the treatment of MG in humans. We therefore tested the potential of a syngeneic fragment and of long synthetic peptides to suppress EAMG. We found that a syngeneic fragment corresponding to the extracellular region of the rat AChR α subunit was as effective as the formerly described human xenogeneic fragment in suppressing ongoing EAMG. This is encouraging in view of the potential use of mucosally administered recombinant AChR fragments for the treatment of MG in humans. However, in severely affected individuals, this antigen‐specific approach may need to be supported by direct modulation of cytokines and costimulatory factors known to be involved in the pathogenesis of EAMG. To test the potential of this approach, myasthenic rats were injected by antibodies either to the proinflammatory cytokine IL‐18 or to the costimulatory factor CD40L. These treatments act via different mechanisms, but both lead to the alleviation of clinical symptoms even when given at the chronic phase of EAMG. We suggest that antagonists to key cytokines and/or costimulatory factors be used to augment antigen‐specific treatments of myasthenia such as mucosal administration of AChR recombinant fragments.
Future Therapeutic Strategies in Autoimmune Myasthenia Gravis
Authors: PSARIDI‐LINARDAKI LOUKIA , MAMALAKI AVGI , TZARTOS SOCRATES J.
Published: January 2004

Abstract: Antibodies against muscle acetylcholine receptor (AChR) undoubtedly play a critical role in the pathology of most myasthenia gravis (MG) cases. Selective elimination of the majority of these antibodies should result in a considerable improvement of the MG symptoms. Such a specific elimination could be achieved by AChR‐based immunoadsorbents. However, sufficient quantities of native human AChR are not available while bacterially expressed recombinant domains of the AChR are unable to bind satisfactorily MG antibodies. We have undertaken the production of the extracellular domains of human AChR subunits in eukaryotic systems, in native‐like conformation, for their use as potent immunoadsorbents. The N‐terminal extracellular domain (amino acids 1–210; α1–210) of the α1 subunit of the human muscle AChR was expressed in the yeast Pichia pastoris. The polypeptide was water‐soluble, glycosylated, and in monomer form. The α1–210 bound 125I‐α‐bungarotoxin (125I‐α‐BTX) with a high affinity (Kd= 5.1 ± 2.4 nM), and this binding was blocked by unlabeled d‐tubocurarine and gallamine. Several conformation‐dependent anti‐AChR antibodies were able to bind α1–210 as did antibodies from a large proportion of MG patients. The purified protein was subsequently immobilized on Sepharose‐CNBr and was used to immunoadsorb anti‐AChR antibodies from 64 MG sera. It eliminated more than 50% (50–94%) of the anti‐AChR antibodies in 20% of the sera, whereas from another 30% of the sera it eliminated 20–60% of their anti‐AChR antibodies. Work is in progress for the expression of the extracellular domain of all other muscle AChR subunits. It is expected that their combined use may eliminate the great majority of the anti‐AChR antibodies from most MG patients.
The Self as a Responding—and Responsible—Artifact
Authors: DENNETT DANIEL C.
Published: January 2004

Abstract: The powerful illusion of a unified, Cartesian self responsible for intentional action is contrasted with the biologically sounder model of competitive processes that yield an only partially coherent agency, and the existence of the illusion of self is explained as an evolved feature of communicating agents, capable of responding to requests and queries about their own decisions and actions.
Whatever Happened to the Soul?
Authors: MURPHY NANCEY
Published: January 2004

Abstract:Traditional religious teachings about the nature of the person, especially body‐soul dualism, influence majority views of the self. Following a historical overview, it is argued that a purely physicalist account of human nature is equally compatible with contemporary science and with Christian thought. However, an account that reduces higher human capacities to neurobiology is unacceptable from a theological perspective.
Out of Contact, Out of Mind
Authors: TURK DAVID J. , HEATHERTON TODD F. , MACRAE C. NEIL , KELLEY WILLIAM M. , GAZZANIGA MICHAEL S.
Published: January 2004

Abstract: A truly remarkable aspect of human existence is the unitary sense of self that exists across time and place. Understanding the nature of self—what it is and what it does—has challenged scholars since antiquity. How can empirical research measure what it is to have a sense of self? We propose that the sense of self may emerge from the functions of a left hemisphere “interpreter” (Gazzaniga, 2000). First, we examine evidence for the existence of self‐processing mechanisms in the intact brain, from behavioral and functional neuroimaging research. The available evidence suggests that the sense of self is widely distributed throughout the brain. Second, we discuss these findings in relation to what is known about higher cognitive functions in humans who have undergone a surgical procedure to sever the connection between the two cerebral hemispheres. Split‐brain research has facilitated an understanding of the way in which each cerebral hemisphere independently processes information. Research in this area has shown that each cerebral hemisphere features distinct information‐processing capabilities. This cognitive asymmetry is reflected in the notion of a left hemisphere interpreter module which, we have argued, generates a unitary sense of consciousness even in the disconnected brain. This chapter describes how this interpreter may also give rise to a unified sense of self.
The Emergence of Consciousness and Its Role in Human Development
Authors: LEWIS MICHAEL
Published: January 2004

Abstract: In this paper, I talk about several issues in regard to self and consciousness. I do so from a developmental perspective, since such a perspective may provide a framework to help understand consciousness as seen in the adult human. Briefly, the two processes I will call the machinery of the self and the mental state of the idea of me develop over the first two years of the child's life. Moreover, and perhaps of equal importance is the fact that the development of consciousness (the idea of me) provides the scaffolding for the development of the child's social and emotional development and is the first step in the child's development of other mental states, which provide the underpinning of a theory of mind. I will first explore what a self is and what it is not; then I will present a developmental model that provides a way of measuring early the idea of me or consciousness. Having shown how to measure this mental state, I will show how it has an impact on the development of a theory of mind, as well as on the child's emotional and social life. Finally, I will turn to the emergence of explicit and implicit consciousness.
Theory of Mind and the Self
Authors: HAPPÉ FRANCESCA
Published: January 2004

Abstract:This paper will discuss one aspect of the self, the ability to reflect on one's own inner states, in relation to recent work on the cognitive and neural basis of “theory of mind.” Are the same representational resources required for “reading” one's own and other minds? Relevant literature from the study of normal development of theory of mind will be reviewed, along with research on a developmental disorder characterized by an apparent inability to think about thoughts: autism. Functional neuroimaging studies of theory of mind will be discussed as will studies that may tap the neural basis of self‐reflection. From these different strands of evidence the speculative suggestion will be made that reflecting on one's own thoughts is not a privileged process, but rather relies on—and may have evolved from—the same cognitive and neural functions used for attributing thoughts to others.
Implicit Self and Identity
Authors: DEVOS THIERRY , BANAJI MAHZARIN R.
Published: January 2004

Abstract: Recent advances in research on implicit social cognition offer an opportunity to challenge common assumptions about self and identity. In the present article, we critically review a burgeoning line of research on self‐related processes known to occur outside conscious awareness or conscious control. Our discussion focuses on these implicit self‐related processes as they unfold in the context of social group memberships. That is, we show that group memberships can shape thoughts, preferences, motives, goals, or behaviors without the actor's being aware of such an influence or having control over such expressions. As such, this research brings to the fore facets of the self that often contrast with experiences of reflexive consciousness and introspection. Far from being rigid or monolithic, these processes are highly flexible, context‐sensitive, and deeply rooted in socio‐structural realities. As such, work on implicit self and identity renew thinking about the interplay between the individual and the collective.
Cultural Selves
Authors: QUINN NAOMI
Published: January 2004

Abstract: Recent cross‐cultural studies of child development reveal that child rearing, while strikingly culturally variable, is everywhere designed to make the child's experience of important lessons constant, to link those lessons to emotional arousal, and to connect them to evaluations of the child's goodness and badness. These claims are illustrated from research on Americans, Chinese, Germans, Gusii (Kenya), Ifaluk (Micronesia), and Inuit (Baffin Island). These three universal features of child rearing accomplish what is a highly specialized task. Constancy of experience alters synaptic connections to grant the pattern of their firing especially high‐resolution, so that the lessons to be learned are unmistakable ones. Accompanied by emotional arousal, these lessons are especially motivating and unforgettable. Brought home with evaluations of the learner's goodness and badness, these lessons are even more motivating and unforgettable. Children get the point of the lesson, enact it once they get it, and remember to enact it on subsequent occasions. Cultural models of child rearing, thus, exploit the neural capacities of the children so reared, to achieve a result, human adulthood, that could not be accomplished by the human brain alone. From exposure to these practices result distinctive cultural selves. These selves are partly implicit, based on the largely unmarked practices designed to make children's experience of important lessons constant and these lessons arousing, and partly explicit, based on the labeling and other marking that connects these lessons to evaluations of children's goodness and badness. The conscious, self‐reflective self that emerges from such explicit evaluation lays the basis for identity—everywhere profoundly culturally shaped, infused with powerful evaluative meanings, and itself highly motivating.
The Mind's Self‐Portrait
Authors: WEGNER DANIEL M.
Published: January 2004

Abstract:Scientific psychology and neuroscience are taking increasingly precise and comprehensive pictures of the human mind, both in its physical architecture and its functional processes. Meanwhile, each human mind has an abbreviated view of itself, a self‐portrait that captures how itthinksit operates, and that therefore has been remarkably influential. The mind's self‐portrait has as a central feature the idea that thoughts cause actions, and that the self is thus an origin of the body's actions. This self‐portrait is reached through a process of inference ofapparent mental causation, and it gives rise to the experience that we are consciously willing what we do. Evidence from several sources suggests that this self‐portrait may often be a humble and misleading caricature of the mind's operation—but one that underlies the feeling of authorship and the acceptance of responsibility for action.
Renovating the House of Being
Authors: MAURON ALEX
Published: January 2004

Abstract: In recent years, the views of the German philosopher Peter Sloterdijk about humanism and the biological self‐engineering of mankind caused much turmoil in European intellectual circles. However, this is just one episode in a more general current controversy about the ethics of self‐manipulation, a debate that often centers around the recent progress in genomics and the possibility of shaping human genetic structure. The complete sequencing of the human genome has reinforced this focus. Making the human genome the object of a highly visible world‐wide research effort has reinforced popular notions stressing the centrality of the genome in defining individuality and humanity. As a result, proponents and opponents of the self‐engineering of human nature have often concentrated on technologies related to the genome. However, if one compares “genome‐based” and “brain‐based” explanations of Self and behavior, it turns out that neural aspects of human nature are more directly relevant. Many philosophical and ethical questions traditionally raised about genetics and genomics acquire more relevance and urgency when re‐examined in the context of neuroscience.
Feelings of Emotion and the Self
Authors: DAMASIO ANTONIO
Published: January 2004

Abstract: The self is a critical component of consciousness. The neural correlates of self have proven elusive, but it is reasonable to suggest that, in its simplest form, the self process requires a composite representation of the ongoing state of the organism as reflected in subcortical and cortical somatic maps within the central nervous system. The basis for these maps is a wealth of signals originating in different sectors of the body‐proper. Some of these signals portray the actual state of the body as modified by emotions in response to interactions with the environment; but other signals are the result of internal simulations controlled from other regions of the central nervous system.
The Computational Self
Authors: SEJNOWSKI TERRENCE
Published: January 2004

Abstract: Your brain is never at rest. Shifting patterns of activity course through your brain at night as you review the events of the day and plan the next day before falling asleep. Rumination is a reflection of the Self that is not directly driven by sensory stimuli. When we record from single neurons in the brain, we discover that even in the absence of sensory stimulation, neurons are continuously active. This is called maintained, or spontaneous, activity, and although it is well documented, it has not been as well studied. Most experiments are designed to look for signals that are elicited by sensory stimuli above the background, without mentioning whether the background has changed too, as it often does. New methods have been developed recently that allow us to study the brain's spontaneous activity and to explore how it might provide clues to the origin and nature of the Self.
A Parallel Between Radical Reductionism in Science and in Art
Authors: KANDEL ERIC R. , MACK SARAH
Published: January 2004

Abstract: Neural science represents an important bridge between the natural sciences concerned with the nature of the physical world and the humanities concerned with the nature of human existence. We try to illustrate this bridging function in two ways. One, we show that many neural scientists study the brain to address humanistically important questions about the mind first raised by classical philosophy. Second, in certain instances the humanities and neural sciences use common methodologies to achieve their respective goals.
The Self
Authors: LeDOUX JOSEPH
Published: January 2004

Abstract: Can we find a way of thinking about the self that is compatible with modern neuroscience? I think we can. First of all, we have to recognize that “the self” is not the same as “the conscious self,” since much of who we are as individuals takes place out of conscious awareness. Second, we have to accept that some aspects of the self, especially the unconscious aspects, occur in and can be studied in other species, allowing us to relate these aspects of the self to detailed brain mechanisms. Finally, it also helps to think of the self in terms of memory. Obviously, much of who we are is based on memories learned through personal experience, including both conscious or explicit memories and unconscious or implicit memories. This is particularly important since much progress has been made in relating memory to the cells and synapses of the brain. By viewing the self as a network of memories the effort to relate the self to the brain can build on this progress. Emphasizing memory and experience does not take away from the fact that our genetic history also contributes to who we are. In fact, genes and experience, or nature and nurture, are, in the end, not different things, but different ways of doing the same thing—wiring the synapses of our brain. In many ways, the self is synaptic. This synaptic view of the self is not meant as a challenge to other views, such as spiritual, cultural, or psychological views. It is instead, just a way of understanding how these other aspects of who we are relate, deep down, to the brain.
Conclusions: From Self‐Knowledge to a Science of the Self
Authors: DEBIEC JACEK , LeDOUX JOSEPH E.
Published: January 2004

Abstract: Traditional accounts of the self represented in religion, literature, philosophy, and other branches of the humanities, are grounded in the subject's personal introspections. This source of knowledge has had a profound impact on terminology, concepts, and theories of the self. By contrast, the scientific method, which uses observational and experimental data, is aimed at objective analyses. The scientific approach to the self, by its very nature, is distinct from the approach in the humanities, and therefore reveals a different view of the self, and sparks new debate about what the self really is. Moreover, different scientific disciplines, spanning the natural and social sciences, investigate different levels of organization, leading to a multifaceted scientific picture of the self. This conference and volume explored areas where some of the different approaches to the self overlap and will, it is hoped, promote the establishment of a richer, more coherent image of what the self is.
Music and the Brain
Authors: ZATORRE ROBERT J.
Published: January 2004

Abstract:The aim of this paper is to illustrate how studying music from a neuroscience perspective may be a valuable way to probe a variety of complex cognitive functions and their neural substrate. Three different sets of issues are described. First, studies dealing with the brain correlates of musical imagery are discussed. This topic is of interest in that it illustrates how subjective sensations may be studied via objective techniques, and gives insight into neural systems associated with internal phenomena. Second, some findings pertaining to absolute pitch are presented. Absolute pitch is a useful example of a highly specific cognitive skill that is unevenly distributed in the population. Examination of its neural basis helps to understand aspects of memory function and points to ways to explore individual differences in brain organization that underlie differential skills. The final topic, music and emotion, has not been the subject of much systematic research, but it is of great interest because it intersects with a large literature on the neuroscience of affective processing. Findings from some studies indicate that music may engage systems concerned with biological reward, raising interesting but so far unanswered questions about the broader role of music in human experience.
Toward the Neural Basis of Processing Structure in Music
Authors: KOELSCH STEFAN , FRIEDERICI ANGELA D.
Published: January 2004

Abstract:In major‐minor tonal music, chord functions are arranged according to certain regularities. The dominant‐tonic progression, known as an authentic cadence, is often used as a marker of the end of a harmonic progression and has been considered a basic syntactic structure of major‐minor tonal music by several music theorists and music psychologists. We review data from studies in which brain responses to an authentic cadence were compared to those elicited by music‐syntactically inappropriate endings. In event‐related electric brain potentials (recorded with EEG), the inappropriate endings elicit early right anterior negativity (ERAN), which is maximal around 200 ms after the presentation of an inappropriate chord. The ERAN is reminiscent of early anterior negativities elicited by syntactic incongruities during the perception of language. Magnetoencephalographic (MEG) data suggest that the ERAN is generated in the inferior frontolateral cortex, an area known to be crucially involved in the processing of (linguistic) syntax. Interestingly, the ERAN can be recorded in nonmusicians and in children, indicating that the ability to acquire (implicit) knowledge about musical regularities and to process musical information according to this knowledge is a general ability of the human brain. This ability is probably of great importance for the acquisition of language in infants and children.
The Promises of Change‐Related Brain Potentials in Cognitive Neuroscience of Music
Authors: TERVANIEMI MARI , HUOTILAINEN MINNA
Published: January 2004

Abstract: Even when simultaneously performing a task unrelated to sounds, the human auditory cortex can precisely model the invariances of the acoustic environment. Data acquired in a mismatch negativity (MMN) paradigm have shown that temporally and spectrally complex sounds as well as their relations are automatically represented in the human auditory cortex. Furthermore, MMN data indicate that these neural sound representations are spatially distinct from phonetic and musical sounds within and between the cerebral hemispheres. Most MMN studies were conducted in pitch dimension, but temporal aspects of sound processing are also under increasing experimentation. To some extent, musical expertise is also reflected in sound representation accuracy as indexed by the MMN paradigm.
Functional Imaging of Pitch Analysis
Authors: GRIFFITHS TIMOTHY D.
Published: January 2004

Abstract: This work addresses the brain basis for the analysis of pitch and pitch patterns required for normal musical perception. Recent functional imaging experiments are consistent with a hierarchical scheme for the analysis of pitch. Mechanisms in the ascending auditory pathway to the primary auditory cortex allow the representation of the spectral and temporal features of individual notes required for the perception of their pitch. Converging experiments where pitch strength is manipulated in different ways suggest that there may be a “pitch center” in the lateral part of Heschl's gyrus, adjacent to the primary auditory area. The suggestion is that there is a representation in this area that correlates with the perception of pitch rather than a simple mapping of physical stimulus characteristics. The analysis of patterns of pitch such as melodies, as opposed to the pitch of individual notes, involves much more distributed processing in the superior temporal lobes and frontal lobes. Involvement of the frontal lobe in pitch pattern analysis may in part reflect whether subjects analyze the pitch patterns in order to carry out an output task.
Music Agnosia and Auditory Agnosia
Authors: VIGNOLO LUIGI A.
Published: January 2004

Abstract: A review and an experimantal study were carried out in search of dissociations between the recognition of music (music agnosia) and that of environmental sounds (auditory agnosia) in stroke patients. The review focused on 45 adequately studied cases published since 1883. The experimental study consisted of administering standard tests of music and environmental sound recognition to 40 unselected patients with unilateral stroke. Among case reports, music was selectively impaired more frequently than environmental sounds, whereas the reverse occurred in the experimantal study. In this, right hemisphere lesions tended either to disrupt the apperception of environmental sounds, sparing music entirely, or to disrupt both environmental sounds and melody, sparing rhythm, whereas left hemisphere lesions tended to spare melody and to disrupt rhythm, either selectively or in association with the semantic identification of environmental sounds.
Varieties of Musical Disorders
Authors: PERETZ ISABELLE , CHAMPOD ANNE SOPHIE , HYDE KRISTA
Published: January 2004

Abstract:Multiple disorders of musical abilities can occur after brain damage. Conversely, early brain anomalies or vast brain injuries may sometimes spare ordinary musical skills in individuals who experience severe cognitive losses. To document these incidences, comprehensive behavioral testing is required. We propose to use the Montreal Battery of Evaluation of Amusia (MBEA) because it is arguably the best tool currently available. Over the last decade, this battery was developed and validated in populations with brain damage of various etiologies. Furthermore, the MBEA is theoretically motivated and satisfies important psychometric properties. It is sensitive, normally distributed, reliable on test‐retest, and correlates with Gordon'sMusical Aptitude Profile, another more widely used battery of tests. To promote its wide usage, the MBEA is now available upon request. In addition, individual MBEA data of 160 normal participants of variable age and education have been made available to all via the internet.
Music and the Brain
Authors: WIESER HEINZ GREGOR
Published: January 2004

Abstract: Studies are reviewed from the perspective of a neurologist and epileptologist interested in “music and the brain.” At the neurocognitive level, deficits in pitch discrimination of patients with brain lesions and those during the intracarotid amobarbital test are outlined, because they show that the temporal lobe and, in particular, the right acoustic cortex are crucial. Hallucinations of music during epileptic seizures as well as the analysis of musicogenic epilepsy point to the same gross localization and lateralization. At the esthetic level, music theoretical concepts on the consonance‐dissonance dichotomy and related EEG examinations are reported, which illustrate the importance of mesiolimbic temporal lobe structures for the pleasure that we might experience when listening to music. The complex interaction of many neuronal circuits and assemblies of both hemispheres in musical perception and performance is illustrated by musical analysis of a recording by an organ player who experienced a right temporal lobe seizure. This analysis revealed that the seizure‐induced errors of the left hand were compensated with the right hand in a musically meaningful way.
Exploring the Influence of Cultural Familiarity and Expertise on Neurological Responses to Music
Authors: DEMOREST STEVEN M. , MORRISON STEVEN J.
Published: January 2004

Abstract:Contemporary music education in many countries has begun to incorporate not only the dominant music of the culture, but also a variety of music from around the world. Although the desirability of such a broadened curriculum is virtually unquestioned, the specific function of these musical encounters and their potential role in children's cognitive development remain unclear. We do not know if studying a variety of world music traditions involves the acquisition of new skills or an extension and refinement of traditional skills long addressed by music teachers. Is a student's familiarity with a variety of musical traditions a manifestation of a single overarching “musicianship” or is knowledge of these various musical styles more similar to a collection of discrete skills much like learning a second language? Research on the comprehension of spoken language has disclosed a neurologically distinct response among subjects listening to their native language rather than an unfamiliar language. In a recent study comparing Western subjects' responses to music of their native culture and music of an unfamiliar culture, we found that subjects' activation did not differ on the basis of the cultural familiarity of the music, but on the basis of musical expertise. We discuss possible interpretations of these findings in relation to the concept of musical universals, cross‐cultural stimulus characteristics, cross‐cultural judgment tasks, and the influence of musical expertise. We conclude with suggestions for future research.
Analysis and Modeling of Expressive Intentions in Music Performance
Authors: DE POLI GIOVANNI
Published: January 2004

Abstract: A performer can convey different expressive intentions when playing a piece of music. Perceptual and acoustic analysis of expressive music performances attempts to understand the musicians' strategies. Moreover, models for rendering different expressive intentions were developed for both analysis and deeper multimedia products fruition.
Musicians versus Nonmusicians
Authors: LOPEZ LUISA , JÜRGENS REINHART , DIEKMANN VOLKER , BECKER WOLFGANG , RIED SIBILLE , GRÖZINGER BERTA , ERNÉ SERGIO NICOLA
Published: January 2004

Abstract: The ability to perceive sounds and correctly categorize them within a scale is the result of the interaction between inherited capabilities and acquired rules. If a subject listens to a melody, occasional and unexpected endings of the melody typically evoke characteristic auditory evoked responses in the latency range of 300‐400 ms (P300). Also, earlier stages of auditory information processing have been exhaustively investigated by means of mismatch negativity (MMN), a deflection that occurs in the auditory evoked response at a latency of about 200 ms, whenever a deviance is randomly inserted in a series of otherwise equal stimuli. Conceivably, perceptual deviations could also be detected against expectancies that are based on abstract rules; introspective experience suggests that such deviations may also elicit fast intuitive responses that typically initiate processes of analytical reasoning for confirmation. In music, the physical features of the stimulus are, in fact, always changing, because the melodic contour consists of a series of notes with different pitch characteristics. In such a condition, a typical mismatch negativity would not be evoked on the basis of physical deviance, but rather of criteria involving the musical contour of the stimulus. In this study, 20 healthy subjects (10 nonmusicians and 10 musicians) underwent auditory stimulation (tone, chord, chord sequence, Mozart and Bach melodies) and both electrical and magnetic recordings. Clear N1 was recorded for all paradigms, in all subjects; MMN and P300 were also recorded, and their amplitudes and latencies were significantly correlated with the musicality score and with the paradigm's difficulty.