1976 — 1978 |
Bellugi, Ursula Klima, Edward (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Formational Constraints On Language in a Visual Mode @ The Salk Institute For Biological Studies |
1 |
1978 — 1981 |
Bellugi, Ursula Klima, Edward (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Structured Use of Space and Movement in a Visual-Manual Language @ The Salk Institute For Biological Studies |
1 |
1981 — 1993 |
Bellugi, Ursula |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
The Structured Use of Space and Movement in a Visual-Manual Language @ The Salk Institute For Biological Studies |
1 |
1985 — 1988 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Acquisition of Morphological Processes in Asl @ Salk Institute For Biological Studies
The general objective of our research is to study the human capacitu for language. We aim to investigate to what extent the overall form and organization of language is determined by the articulatory and perceptual modality in which it has developed, and to what extent these represent more fundamental aspects of human cognition. As a research tool we study American Sign Language (ASL), the system of hand signs developed by deaf people in the absence of speech. We find that ASL differs dramatically from English and other spoken languages in some of the mechanisms by which its lexical units are modified. For the form of its inflectional and derivational processes the mode in which the language develops makes a crucial difference. In this grant we propose to study the acquisition of three contrasting subsystems of American Sign Language: 1) The system of morphological processes which operate on signs, simultaneously changing or adding specifications for dimensions of movement to the root form of the sign. 2) Compounding processes which are essentially sequential combinations of signs, bound together by particular rhythmic properties which differentiate them from phrases. 3) Spatial indexing, a system which includes the establishment of loci for non-present referents in the signing space between signer and addressee, and anaphoric reference by pointing or by inflection of verb. Detailed longitudinal studies of spontaneous mother/child interactions on videotape are augmented with experimental interventions. We have chosen to investigate the acquisition of specific aspects of the grammar, selected so that some are most like and some are most unlike comparable processes in spoken language. In the process, we investigate the acquisition of some of the most distinctive aspects of signed languages: its conflation, its simultaneity and its structured use of space. The comparison of the acquisition of signed and spoken languages becomes a priviledged ground for testing hypotheses about the mechanisms that determine language structure.
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1 |
1985 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Psycholinguistics of American Sign Language Morphology @ Salk Institute For Biological Studies
The general objective of our research is to study the human capacity for language. We aim to investigate to what extent the overall form and organization of language is determined by the articulatory and perceptual modality in which it has developed and to what extent they represent more fundamental aspects of human cognition. As a research tool we study American Sign Language, the system of hand signs developed by deaf people in the absence of speech. We find that ASL differs dramatically from English and other spoken languages in some of the mechanisms by which its lexical units are modified. For the form of its inflectional and derivational processes the mode in which the language develops makes a crucial difference. The primary focus of the present grant is to bring psycholinguistic evidence to bear on an understanding of the structural properties of a language in a different mode. We propose some experimental investigations of the morphology of ASL, bringing into relief the interplay between cognitive processing and linguistic form, addressing specific issues not only relevant to the ways deaf signers process morphological forms in ASL but, more generally, relevant to theories of the perception of speech and to theories of the representation of language in the brain. We proceed along four major lines of inquiry. 1) We first explore whether signers encode modulated forms separately in terms of their component morphemes even through lexical and grammatical elements are simultaneously encoded in a sign form. 2) We then address whether signers utilize modulatory features, such as those that have emerged from our linguistic analysis, during the perception and memory of modulatory forms. 3) We further begin exploration of the virtually uncharged area of the phonetics of modulatory movement. We aim to uncover physical correlates that are sufficient for the perception of proposed featural distinctions. This research will allow us for the first time to adequately address the issue of categorical perception for changes along temporal dimensions of ASL modulations. 4) We propose studies on whether processing of certain modulatory features is categorical, as has been found for many speech sounds, or is continuous, as is the case for most psychological continuations. Finally, we examine cerebral asymmetries for specifically grammatical processing of ASL modulations, provid (Text Truncated - Exceeds Capacity)
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1 |
1985 — 1993 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Brain Organization: Clues From Sign Aphasia @ Salk Institute For Biological Studies
The general objective of our research is to study the biological foundations of human language. We investigate language and its formal architecture, as well as its representation in the brain by studying languages which have arisen outside of the mainstream of spoken languages: the visual gestural systems developed among deaf people. American Sign Language (ASL) displays complex linguistic structure, but unlike spoken languages, conveys much of its structure by manipulating spatial relations, thus exhibiting properties for which each of the hemispheres of hearing people shows a different predominant functioning. The study of deaf signers with left or right hemisphere damage offers a particularly revealing vantage point for understanding the organization of higher cognitive functions in the brain, and how modifiable that organization may be. We propose four major series of experimental studies, each focusing on a special property of the visual gestural modality as it bears on the investigation of brain organization for language: 1) The Role of the Left Hemisphere for ASL Grammar. We propose an in depth evaluation of deaf signers having either left or right brain damage. WE will investigate the relative contributions of each of the cerebral hemispheres to left or right brain damage. We will investigate the relative contributions of each of the cerebral hemispheres to language, with special reference to the linguistic functions and the spatial mechanisms that convey them. Specifically, we will examine the functioning of the two cerebral hemispheres for differential uses of space in ASL; from spatially organized syntax to the use of articulatory sign-space to represent external world-space. A variety of techniques will be brought to bear, including the investigation of the moment to moment on-line construction of linguistic and spatial mental representations. 2) The Role of the Right Hemisphere in Extra-Syntactic aspects of ASL. In sign language, facial signals serve two opposing functions: specifically linguistic as well as effective. Pitting form against function, we will investigate whether these two different functions are differentially lateralized in ASL. 3) Brain Organization for Spatial Cognition and Imagery. Since spatial relations and linguistic relations are so intimately intertwined in ASL, we will examine brain organization for nonlanguage for nonlanguage spatial functions, asking whether the two cerebral hemispheres in deaf signers show differential specialization. Paradigms will be developed that allow experimental investigators of attentional functions, and assess capacities for components of imagery, as imagery may play a unique role in sign language syntax and discourse. 4) Neural Mechanisms for Sign Language. We will investigate the dissociability apraxia from sign aphasia through experiments designed to separately evaluate impairments in linguistic, symbol and motor functions as well as to analyze the neural correlated for sign language, Summary. The essential issue and heart of this proposal is the nature of cerebral specialization for a visual- gestural language. By illuminating this issue we hope to shed light on theoretical questions concerning the determinants of brain organization for language general.
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1 |
1986 — 1988 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Bilingualism, Hemispheric Specialization &Lang. Deve. @ Salk Institute For Biological Studies
The general objective of our research is to study the biological foundations of human language. We aim to investigate language and its formal architecture, as well as its representation in the brain, by studying languages which have arisen outside of the mainstream of spoken languages, the visual-gestural language of deaf people. For the form of its grammatical devices, the modality in which a language develops makes a crucial difference. Multi-layering of linguistic elements and the use of space in the service of syntax appear to be modality-determined aspects of sign language. One of the central issues in the renewal grant is the consequences of the differing capacities of visual and auditory processing on the form that language takes and thereby on the nature of mental representations involving language, and on the nature of language representation in the brain. We proceed along three major lines of inquiry: 1) We investigate linguistic and modality determinants of perception through the computergraphic presentation of movement isolated from sign forms. We analyze the psychological representations of human movement and the effect on that representation when movement constitutes part of a linguistic system. We then turn to spatial vs. temporal processing and examine mental representations of sign language syntax. 2) To assess the generality of the putative modality-determined characteristics of visual-gestural languages, we propose structual and psycholinguistic studies of Chinese Sign Language, a sign language completely unrelated to American Sign Language. We combine these cross-linguistic studies with studies of the structure and processing of Chinese characters, a script which, like sign, puts heavy emphasis on visual-spatial processing. 3) Finally, we investigate the nature of hemispheric specialization for language by pitting physical form against linguistic function for language in another modality.
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1 |
1989 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Spatial Cognition and Spatial Language @ Salk Institute For Biological Studies
The general objective of our research is to study the human capacitu for language. We aim to investigate to what extent the overall form and organization of language is determined by the articulatory and perceptual modality in which it has developed, and to what extent these represent more fundamental aspects of human cognition. As a research tool we study American Sign Language (ASL), the system of hand signs developed by deaf people in the absence of speech. We find that ASL differs dramatically from English and other spoken languages in some of the mechanisms by which its lexical units are modified. For the form of its inflectional and derivational processes the mode in which the language develops makes a crucial difference. In this grant we propose to study the acquisition of three contrasting subsystems of American Sign Language: 1) The system of morphological processes which operate on signs, simultaneously changing or adding specifications for dimensions of movement to the root form of the sign. 2) Compounding processes which are essentially sequential combinations of signs, bound together by particular rhythmic properties which differentiate them from phrases. 3) Spatial indexing, a system which includes the establishment of loci for non-present referents in the signing space between signer and addressee, and anaphoric reference by pointing or by inflection of verb. Detailed longitudinal studies of spontaneous mother/child interactions on videotape are augmented with experimental interventions. We have chosen to investigate the acquisition of specific aspects of the grammar, selected so that some are most like and some are most unlike comparable processes in spoken language. In the process, we investigate the acquisition of some of the most distinctive aspects of signed languages: its conflation, its simultaneity and its structured use of space. The comparison of the acquisition of signed and spoken languages becomes a priviledged ground for testing hypotheses about the mechanisms that determine language structure.
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1 |
1989 — 1998 |
Bellugi, Ursula |
R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Language Modality and the Brain @ Salk Institute For Biological Studies |
1 |
1989 — 1990 |
Bellugi, Ursula |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissociations Between Language and Cognition: Evidence From a Neurodevelopmental Disorder @ The Salk Institute For Biological Studies
ABSTRACT The general objectives of the research are to understand the interrelationship and separability of language and cognition. Williams Syndrome (WS), a rare (est. 1:50,000) metabolic disorder provides a unique and powerful vehicle for investigating separa- bility of higher cortical functions. Preliminary studies with six WS adolescents suggest a specific behavioral profile which is discontinuous from normal; subjects are mentally retarded with grammatical capacity remarkably spared. The broad program of studies outlined below will provide a new and important perspec- tive on the neural basis for language and cognition. I. Decoupling of language from cognition The precise relationship between language structure (grammar) and other aspects of cognitive functions is a hotly debated theoretical issue. The study of normal development sheds little light on this issue in that linguistic and nonlinguistic cognitive faculties are so intertwined that it is extremely difficult to separate these functions. In contrast, subjects with WS may provide a unique opportunity to address hypotheses bearing on the dissociability of linguistic and nonlinguistic cognitive domains and their underlying neural basis. II. The selective autonomy of syntax The investigators will mount a broad program of probes of syntax and semantics, using both on-line and off-line tasks which may show fractionation of higher cortical functioning. They will examine the degree to which linguistic components are vulnerable to marked cognitive deficits. The preliminary hypothesis is that language in WS subjects may be characterized by the relative preservation of the most autonomous aspects of the linguistic system (syntax), and that to the extent that other cognitive systems interact with a component of the linguistic system, e.g. in the semantic domain, increasing deviance in language organiza- tion may be found. The selective preservation of grammar in this population would provide an important testing ground for determi- nants of cerebral specialization for language. III. Differential impairment in components of spatial cognition Spatial cognition has traditionally resisted fractionation into components; however, WS may provide a strong case for dis- sociations within this domain. The investigators will explore the hypothesis that WS results in severely impaired visuospatial abilities, but preserved visuoperceptual capacities. In addition, preliminary studies suggest that spatial cognition in WS is characterized by a selective attnetion to details of a configuration at the expense of the whole.
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1 |
1990 — 1993 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development of Spatial Language and Spatial Cognition @ Salk Institute For Biological Studies
The general objective of our research is to study the human capacitu for language. We aim to investigate to what extent the overall form and organization of language is determined by the articulatory and perceptual modality in which it has developed, and to what extent these represent more fundamental aspects of human cognition. As a research tool we study American Sign Language (ASL), the system of hand signs developed by deaf people in the absence of speech. We find that ASL differs dramatically from English and other spoken languages in some of the mechanisms by which its lexical units are modified. For the form of its inflectional and derivational processes the mode in which the language develops makes a crucial difference. In this grant we propose to study the acquisition of three contrasting subsystems of American Sign Language: 1) The system of morphological processes which operate on signs, simultaneously changing or adding specifications for dimensions of movement to the root form of the sign. 2) Compounding processes which are essentially sequential combinations of signs, bound together by particular rhythmic properties which differentiate them from phrases. 3) Spatial indexing, a system which includes the establishment of loci for non-present referents in the signing space between signer and addressee, and anaphoric reference by pointing or by inflection of verb. Detailed longitudinal studies of spontaneous mother/child interactions on videotape are augmented with experimental interventions. We have chosen to investigate the acquisition of specific aspects of the grammar, selected so that some are most like and some are most unlike comparable processes in spoken language. In the process, we investigate the acquisition of some of the most distinctive aspects of signed languages: its conflation, its simultaneity and its structured use of space. The comparison of the acquisition of signed and spoken languages becomes a priviledged ground for testing hypotheses about the mechanisms that determine language structure.
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1 |
1990 — 1994 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Fractionations Between Language and Cognition @ Salk Institute For Biological Studies
cognition disorders; cognition; metabolism disorder; language; syndrome; child mental disorders; language disorders; neuropsychological tests; neurophysiology; Downs syndrome; brain interhemispheric activity; adolescence (12-20); semantics; mental retardation; developmental neurobiology; neuropsychology; mental process; human subject; electrophysiology;
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1 |
1992 — 2003 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Brain Organization--Clues From Sign Aphasia @ Salk Institute For Biological Studies
The general objective of our research is to study the neurobiology of language. American Sign Language (ASL) displays complex linguistic structure, but unlike spoken language conveys much of its structure by manipulating spatial relations. Space is used in ASL in a multifunctional way: (l) to encode grammatical relations within individual signs (phonology & morphology) and among those signs within a sentence (syntax); (2) to encode discourse relations among the referents in a discourse across sentences; and (3) to encode spatial relations themselves in the context of describing spatial layouts. We propose to explore the properties of each of these uses of space in ASL, their interaction, how they relate to non-linguistic spatial cognition, and their underlying neurobiology. Left Hemisphere Organization for ASL Grammar. Our research strongly supports a linguistic basis for the left hemisphere specialization for language. In the renewal, we investigate the neural organization of sign language within the left hemisphere. We propose new experiments designed to elucidate the ways in which various grammatical components of ASL break down following brain damage, with emphasis on the unique encoding of grammatical information in ASL (e.g. via facial expression & spatial contrasts). Right Hemisphere Organization for ASL Spatial Discourse. ASL discourse representations are encoded in space, and discourse functions are achieved by manipulations of spatial-discourse frameworks. RHD signers show no signs of aphasia but frequently show impairments at the discourse level. We will use a new tasks to follow up on evidence for a selective impairment of specific components of sign discourse. The Use of Space to Represent Spatial Relations in ASL. Besides using space to represent grammatical and discourse relations, ASL uses space to represent spatial relations themselves. In spatial mapping, the spatial relations among points in signing space map onto real-world spatial relations in an isomorphic fashion. We will investigate the basis of RHD deficit in this area, which contrasts with RHD subjects' unimpaired usage of space for syntactic functions. Brain Organization for Spatial Cognition. We will study the relation between various spatial cognitive functions and the use of space in ASL (discourse & spatial mapping). We will also investigate mental imagery in signers, following up on preliminary indications that signers may show enhancement of specific facets of image manipulation. We will compare performance in deaf signers with hearing non-signers to probe effects of linguistic experience on brain organization for spatial cognition. The Neural Systems Underlying Sign Language: Modality Dependent and Independent Effects. Using a recent dramatic improvement in neuroimaging (BrainVox) that allows 3-D in vivo visualization of brains, we initiate a new program aimed at mapping out the neural systems underlying ASL processing, bearing directly on the issue of neuronal plasticity and the effects of linguistic experience on brain organization.
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1 |
1994 |
Bellugi, Ursula |
R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
Language and Cognition in Williams Syndrome @ Salk Institute For Biological Studies
The focus of the proposed conference will be on the theoretical investigation of language and cognition through a multi-level analysis of Williams syndrome (WMS), a genetically based syndrome in which the major domains of cognitive function show a principled separation. The conference will focus on the implications of this interdisciplinary research for education and language policy. To date, there is no existing forum, society, or organization that brings together investigators from different fields who have specific research on WMS and communication disorders. This professional meeting will provide a much needed forum for presentation and discussion of new developments and collaborative research concerning the linguistic and cognitive profiles of WMS; their origin; development, and biological basis, and the implications of WMS for language an cognition in brain structure, brain function, and at the level of the gene. Additionally, the meeting seeks to attract researchers working in relatively isolated environments who are not aware of each others work, as well as new researchers to the crucial filed of interdisciplinary study of language and communication disorders. Topics and Format The conference topics were selected using two criteria: (1) The existence within the topic of relevant and timely research involving WMS; (2) The relevance of the topic to the biological bases of language and cognition. The six main sessions will include the following topics: (1) Linguistic Profiles in WMS (Issues: delineation of linguistic preservation; the juncture between language and cognition: differential profiles in high functioning WMS individual); (2) Cognitive Profiles in WMS (Issues: peaks and valleys in spatial cognition; identification of islands of sparing in WMS in nonlinguistic cognition; differential trajectories of development in face processing and language; the role of the emergence of grammar); (3) Affect and Temperament in WMS (Issues: affect, emotion, temperament, psychosocial functioning); (4) Brain Structure and Brain Function in WMS (Issue: characteristic brain structure in WMS; callosal morphology and spatial cognition; cerebellar morphology and language; characteristic brain function in WMS; new brain imaging methodologies; histological pathology; distributed brain system models); (5) Molecular Biology of WMS (Issues; genetic etiology; biochemical pathophysiology); (6) Medical Research in WMS: A Developmental Perspective (Issue; treatment and developmental trajectory of abnormal calcium metabolism; hyperactivity and mood disorders during development; effects of drug therapy)' and (7) Round Table: Intersecting Concerns of Researchers, Clinicians, and Educators (Issues: research relevant to clinical and educational concerns methods of information transfer between research and care provider; new research directions).
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1 |
1994 — 1995 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development of Spatial Language and Cognition @ Salk Institute For Biological Studies |
1 |
1996 — 2003 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Williams Syndrome: Bridging Cognition and Genes @ Salk Institute For Biological Studies |
1 |
1996 — 2002 |
Bellugi, Ursula |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Developmental Profiles of Williams Syndrome Children @ University of California San Diego
The long-term goal of our research is to understand the biological bases of development of language and other cognitive functions. We have been investigating Williams syndrome, a rare genetically-based disorder that results in mental retardation. We have found that the syndrome also results in specific dissociations in cognitive functions, both within and across domains; (a) massive cognitive deficits but considerable sparing of language in adolescents and adults; and (b) extreme disorders in spatial cognition but excellent face processing. Moreover, our studies are finding that Williams syndrome leaves a distinctive morphological stamp on the brain, manifest in both neurophysiological and neuroanatomical findings. Contrasts in the Development of Language and Other Cognitive Domains. In the studies proposed here, we will examine developmental trajectories of language and other cognitive domains in Williams syndrome children age 5-12 years. The objective is to describe and compare the development of individual cognitive domains and their underlying neural bases. The study of developmental trajectories in Williams syndrome children can provide a new perspective on the relationships between domains of cognition and brain organization. While there is relative sparing of language (particularly syntax) ion the adolescents,, their language is not without anomalies (e.g., signs of unusual semantic organization). There are also morphological errors that persist. Developmentally, there are also anomalies: the Williams syndrome toddlers exhibit massive delays in language milestones. Our finding so far is that at least certain aspects of language in Williams syndrome do not really start flourishing until 10 years of age or so. One of the objectives of the research is to explore the nature of this selective recovery and to find links between the delay in onset in language and the anomalies that later surface. Intersection of Affect and Language in Discourse in Development. Williams syndrome adolescents make abundant usage of affective linguistic devices in discourse and display strong interest in social interaction. Preliminary observations of Williams syndrome children suggest that this affective profile may appear prior to the emergence of language. We will investigate the links between language and affect in development in this syndrome. Visual Based Cognition in Williams Syndrome: Peaks & Valleys in Development. Williams syndrome results in a highly specific dissociation in spatial cognition in which there is selective attention to details of a configuration at the expense of the whole. In contrast, face processing shows remarkable preservation across experimental paradigms. Thus, Williams syndrome can provide a powerful vehicle for investigating the developmental separability of functions within, as well as across, cognitive domains. Brain Organization in the Developing Williams Syndrome Child. Our research with Williams syndrome children and adolescents suggests that aspects of language and other cognitive functions may be mediated by neural systems that differ in major ways from those seen in normal populations. We will investigate the brain organization through combined measures of behavior and neurophysiology. The study of development in this rare disorder provides major contrasts with other populations studied in the Center. These studies will also provide crucial information for families, physicians and educators.
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0.922 |
1996 — 2000 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core--Statistical and Computer Core @ Salk Institute For Biological Studies
The Administrative/Statistical Services Core has three main functions: to facilitate scientific and administrative communication among the Project participants, to manage the central data archives and facilitate exchange of data among projects, and to coordinate statistical services and consultation for the participating investigators. Specifically, it will provide and maintain resources for data management and analysis, serving the three projects and their interactions. The P.I. will supervise the Administrative, Statistical and Computer interactions. In addition, it has primary responsibility for planning, implementation and overall coordination of the interface between the Cores and the five projects. A central database will be constructed to include the following data partitions: Genetic Probe results, Cell Line samples, Cytoarchitectonic measurements, Event Related Potential and Magnetic Resonance Imaging results and aggregated Neurobehavioral measures. Database connectivity is available via a fiber optic link to the University of California, San Diego Super Computer Center, from which satellite bandwidth provides access to each investigator connected to the Internet this Core A has primary responsibility for database maintenance and construction including security precautions and data entry verification.
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1 |
1996 — 2002 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Williams Syndrome--Neurocognitive Characterization @ Salk Institute For Biological Studies
Our basic goal is to understand the biological bases of language and other cognitive functions. Williams syndrome (WMS) is a genetically-based neurodevelopmental disorder involving mental retardation that displays dissociations both within and across domains: (a) severe cognitive deficits but remarkably spared language; and (b) extreme disorders in spatial cognition but excellent facial processing. These dissociations in higher cognitive functioning make WMS an invaluable paradigm for the study of brain and behavior relationships and the mapping of brain and behavior phenotypes to the genome. Neurocognitive Characterization of WMS: Consistency and Variability. The crucial starting point of this Program Project lies in obtaining cognitive measures of each of the subjects, measured in the context of our existing profile of asymmetric cognitive functioning that distinguishes WMS. Using a Basic Neurocognitive Battery, we characterize the attributes that are relatively stable across all WMS subjects as well as the variability of these attributes; this will allow us to link patterns of co-occurrence across domains of cognitive functioning and across levels from cognition to brain and, ultimately, to the genome. Experiments on Processing Bases of Neurocognitive Dissociations. With a succession of highly focused small group studies, we investigate the basis of the unique cognitive architecture found in WMS. In the domain of language, we examine the integrity of specific aspects of grammatical and semantic processing. In the domain of visual-based functioning, we examine a bases for the extremely impaired spatial processing coupled with the remarkably good facial processing in WMS. Mapping Between Cognition and Brain Bases. Studies of neurophysiology, neuromorphology, and brain cytoarchitectonics conducted by laboratories in this Program Project suggest that neural systems subserving cognitive functions in WMS are different from normal. We will apply bi-directionally motivated analyses of brain-behavior relationships in order to elucidate the neural systems which underlie language and visual-spatial functioning. Mapping phenotype to Genotype in WMS. Our ultimate goal is to begin the search for links between the WMS phenotype, with its associated variability, and the genome. We will pursue this goal through a mapping between phenotypic attributes - - at the levels of cognitive domains, brain function, brain structure, and medical presentation -- and differential patterns of deletion on chromosome 7 manifested by our WMS population. Relationships across levels may shed valuable light on the genetic foundations of the asymmetric neurocognitive profile of WMS. In general, our studies with this genetically-based neurodevelopmental disorder will provide new opportunities to explore some of the central issues of cognitive neuroscience that tie cognitive functions to brain organization, as well as to their genetic bases.
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1 |
1997 — 2001 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Williams Syndrome: Bridging Cognition and Genes @ Salk Institute For Biological Studies
The overall aim of this Program Project is to build bridges between cognition, brain and gene. Williams syndrome (WMS), a rare genetically- based disorder, results in mental retardation, distinctive facies, and a specific heart defect. In studies of WMS subjects, we have found that the syndrome may also result in specific dissociations in cognitive function, both within and across domains: (a) massive cognitive deficits but remarkably spared language; and (b) extreme disorders in spatial cognition but excellent facial processing. Moreover, we have found that WMS leaves a distinctive morphological stamp on the brain, manifested in both neurophysiological and neuroanatomical findings. Recently, WMS has been shown to be associated with a hemizygous deletion around the elastin gene on chromosomal, locus 7q11. This finding permits on exciting new line of research that may create links from the brain and cognitive sequellae of this rare disorder to its genetic basis, thus extending cognitive neuroscience to the level of molecular genetics. In Project I: Neurocognitive Characterization, we will determine the neuropsychological profiles of 100 WMS subjects, using cognitive probes that illuminate apparent markers for the syndrome. Project I will also apply a refined set of probes to characterize the nature and extent of the dissociations within the WMS profile. In Project 2: Neurophysiological Characterization we will use event related potentials to study brain functioning in WMS subjects. In Project III: Neuroanatomic Characterization we will use in vivo magnetic resonance imaging to examine the distinctive brain structure in WMS. We will expand our studies with new high-resolution techniques allowing us to address specific hypotheses on brain/behavior relations in terms of neural systems. In Project 4: Brain Cytoarchitectonic Characterization we will locate and examine brain cytoarchitectonic anomalies in WMS including abnormal neuronal maturation. In Project 5: Molecular Genetic Characterization we will determine the locus and extent of deletion in the region surrounding the elastin gene in each WMS subject in our study, and the locations of candidate genes for the phenotype to genotype mapping. The Program Project is served by two cores: Administrative, Statistical, and Computer Services, and Diagnostic Methods and Services, which will provide Behavioral Diagnostics, Neuroimaging (ERP and MRI), Brain Autopsy samples, and Biological samples. The Program Project will also have available the separate services of the recently established Williams Syndrome Clinic. By coupling the neuropsychological, neuroanatomical, and genetic results of this Program Project, we can contribute to a greater understanding of WMS and, ultimately, of the relationship between, brain structure and function, and the gene.
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1 |
1997 — 2001 |
Bellugi, Ursula |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Neural Sytems and Retrieval of Asl Signs For Concrete Entities/Actions/Spatial
Studies with deaf ASL signers with brain lesions suggest that the neural organization for language in deaf signers is similar to that found in hearing individuals at the gross hemispheric level. What is not known from the lesion studies is the extent to which there are subtle differences in the neural organization of language related systems within the left hemisphere of deaf individuals. The proposed experiments are designed to identify and characterize those aspects of the visual-gestural modality of sign language that may alter the neural basis of lexical retrieval and production. The experiments complement those proposed in Projects 1 and 3, such that direct comparisons can be made between the neural systems involved in retrieving spoken English words and in retrieving manual ASL signs. We will test four principal hypotheses in a series of [150]H2O PET experiments conducted in 60 normal deaf native ASL signers: (1) The retrieval of ASL signs denoting concrete entities belonging to distinct conceptual categories depends upon anatomically separable regions which roughly mirror those found in hearing English speakers. (2) The distribution of neural systems involved in mediation of lexical retrieval of signs for concrete entities can be partially altered when the form of a sign itself is conceptually-based (e.g., as in iconic vs. non-iconic ASL signs, but not when the difference between sign classes is linguistically- based, as in finger spelled vs. native signs). (3) The retrieval of signs for actions with distinct sensory-motor attributes depends upon partially segregated neural systems, and the motorically-based iconicity of ASL signs for actions with the hand/arm may alter this neural distribution. (4) Language modality may partially alter the neural systems involved in the retrieval of certain lexical expressions that refer to spatial relations; specifically, the retrieval of ASL classifier expressions which indicate spatial relations via a direct mapping from physical space to signing space will depend upon neural systems partially segregated from those involved in the retrieval of English and ASL prepositions denoting the same spatial relations. In addition to enhancing our understanding of the neurobiology of sign language (and thus of language itself), the results will be essential for improvements in diagnosis and for the development of rehabilitation strategies in deaf patients.
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0.91 |
2004 — 2009 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Williams Syndrome: Bridging Cognition, Brain and Genes @ Salk Institute For Biological Studies
DESCRIPTION (provided by applicant): The overarching goal of this program project is to build bridges across disciplines, linking higher cognitive functions to their underlying neurobiological bases and their molecular genetic underpinnings using a specific genetic disorder, Williams syndrome (WS). To accomplish this goal, the program combines cognitive, electrophysiological, structural and functional imaging, histological, with molecular genetic approaches to study groups of individuals with WS. The findings of peaks and valleys of abilities in WS, including mild to moderate mental retardation in the context of a specific deficit in visuospatial processing, relative strengths in face processing and certain aspects of language, in addition to hypersociability. This unique profile makes WS an invaluable paradigm for the study of brain and behavior relationships, and for mapping to the genome. Program project: Project II, Neurophysiological Imaging characterizes the electrophysiological signature of the WS brain during sensory and cognitive processing. Project III: Functional Neuroimaging, uses multifaceted imaging techniques (high field-structural, functional, and diffusion tensor imaging) to identify neural pathways involved in WS cognition. Project IV. Molecular and Cellular Architectonics, explores histological and gene expression differences within brain areas associated with the cognitive profile of WS. Project I: Neurocognitive Characterization, will examine cognitive processing mechanisms and map sources of cognitive variability to neural pathways and variations in genetic expression. Studies from each project work interactively using integrated approaches to test hypotheses related to dorsoventral and posterior/anterior gradients in brain development, as well as changes within limbic system pathways as they relate to cognition and behavior. Together, these studies provide new opportunities for illuminating pathways among specific genes, neural systems, and cognitive functions.
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1 |
2004 — 2008 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Neurocognitive Characterization of Williams Syndrome @ Salk Institute For Biological Studies
Individuals with Williams syndrome (WS) have an unusual cognitive profile characterized by visuospatial processing deficits but strengths in face processing, language, and hypersociability. Project V seeks to understand the cognitive processing of WS through the achievement of the following specific aims: Aim 1- Characterization and Expansion of the WS Cognitive Phenotype: We will continue in our successful strategy of administering a core battery of standardized measures of cognitive functioning to groups of WS, normal controls, and individuals with non-specific mental retardation. Our core battery provides the basis for cross-level analyses linking cognition to its cerebral and genetic underpinnings, with special attention paid to individuals with special deletions and differing parent of origin. Aim 2 - Understanding the Processing Bases of Neurocognitive Dissociations in WS. Based on our latest work, and converging information across projects, we have identified three interrelated domains that we believe present the optimal potential for understanding WS cognitive processes: a) Spatial Deficit. Experiments focus on dorsoventral and posterior/anterior processing gradients, including a new investigation of a supramodal spatial deficit by studying auditory localization and auditory-visual sensory integration, b) Face Processin.q Strength. Experiments will help clarify the nature of this relative strength in WS, emphasizing early visual processing influences, face-specific processing strategies, and top-down processing influences, c) Affiliation: Lan.qua.qe, Affect and Empathy. Studies will investigate language and affect processing in coordinated studies with Projects II and III. Aim 3 - Mapping the Cognitive Phenotype to its Neural and Genetic Bases. This Aim is achieved through the coordinated design of studies across Projects I-V. Recent advances across all projects have led to tightly integrated studies addressing identical hypotheses that will provide an unprecedented opportunity for increasing our understanding of the neural and genetic bases of cognition in WS. Summary. This renewal tests exciting new hypotheses linking genetics (e.g., imprinting and deletion size) and neural systems (e.g., cell size and density, overactivity and enlargement of amygdala, etc) to the cognitive phenotype of WS.
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1 |
2004 — 2006 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Brain Organization: Clues From Sign Aphasia @ Salk Institute For Biological Studies
DESCRIPTION (provided by applicant): The overarching aim of this project is to understand the functional neuroanatomy of language and the neurodevelopmental factors that drive that organization. We approach this issue from the perspective of American Sign Language (ASL), a natural language system which includes linguistic structuring similar to that found in spoken language, but which differs radically in terms of sensory and motor modalities. By comparing the neural organization of signed and spoken language, we can explore the effects of modality on the organization of neural networks supporting language in general. Despite the spatialized nature of ASL, our work to date has shown that signed language ability dissociates from non-linguistic spatial and gestural abilities, and relies on many of the same networks implicated in spoken language. Building on these findings, and using a combination of lesion and fMRI methodologies, this proposal focuses on aims in three areas. (1). Neurocognitive Effects of Focal Lesions in Deaf Signers. We aim to build our database of the neurocognitive effects of focal brain injury in deaf signers for both group- and case-study investigations. The database will be a unique resource for a range of theoretical issues. (2). Neural Systems Underlying Sign Language Comprehension. Our aim is to map the neural systems supporting the perception/comprehension of ASL at three levels ("phonemic"/lexical, sentence, and spatialized discourse) and to study their relation to similar non-linguistic perceptual abilities such as motion and form perception, gesture comprehension, and aspects of spatial processing. (3). Neural Systems Underlying Sign Language Production. The aim is to map the neural systems supporting ASL production at these three levels and its relation to non-linguistic manual output and to ASL perception. These studies will clarify the within-hemisphere organization for sign language as well as address recent lateralization controversies about signed vs. spoken language differences. The proposed studies will provide converging evidence from lesion studies and experiments using functional brain imaging to illuminate the neurobiology of language. Mapping the biological organization of language in general, and of signed languages in particular, is central to the concerns of cognitive neuroscience. The research addresses the extent and limits of neural plasticity. Moreover, these studies may directly benefit clinicians, caregivers, and educators by providing crucial information about deaf individuals with brain damage, as well as pave the way to deeper investigations of the neurobiology of language.
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1 |
2004 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Administrative and Statistical @ Salk Institute For Biological Studies |
1 |
2008 — 2012 |
Bellugi, Ursula |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Social and Affective Components of Communication @ University of California San Diego
The goal of the Program Project as a whole is to study hierarchical levels of neural and cognitive processing in children with neurodevelopmental disorders to better understand the functional organization of these systems. Within this framework, the role of Project 3 will be to systematically examine the neural, psychophysiological, and information processing bases of major differences in social affective behavior in children with neurodevelopmental disorders of different nature and origin. Children with neurodevelopmental disorders often have significant impairments in social adaptation and social communication, which impact their relationships with others. The mechanisms that are implicated in these impairments are poorly understood. The populations selected include genetically based Williams syndrome (WS), behaviorally defined High Functioning Autism (HFA) and Language Impairment (LI), as well as children with Early Unilateral Focal Lesions (FL), contrasted with typically developing (TD) controls. The neurodevelopmental populations chosen include tendencies to extremes in social behavior, from those that are socially avoidant (HFA) to those that are socially driven (WS). In Aim 1, we provide a systematic characterization of sociability and temperament across populations, based on theoretical models. In Aim 2, experimental studies will evaluate autonomic indices of information processing of social vs. non-social, visual and auditory, affective stimuli. A further aim is to examine how differences in underlying sensory/perceptual processing (Project 1) and in spatial attention and working memory (Project 2) are reflected as differences in information processing in the social context. In Aim 3, we evaluate how the characteristic social-affective profiles of the populations (Aims 1, 2) relate to expressivity in social and non-social, language and non-language contexts. We will utilize new tools of investigation for quantifying social and non-social behavior as novel contributions to understanding how aspects of personality reflected in, e.g., narratives, language, and social interaction behaviors, converge with psychophysiological profiles and receptive processing capabilities (Aim 2, Projects 1, 2), and at the level of discourse (Project 4), to provide characterizations both bottom-up and top-down. In Aim 4, we examine the integrity of neural systems underlying social-affective behavior using high-resolution brain imaging across the populations, each at a significant risk for differing problems in social functioning. In these integrated studies, we pursue new lines of investigation that will elucidate long-standing theoretical and clinical issues in differing social-affective profiles of neurodevelopmentally disabled populations. The studies will make a significant contribution toward understanding the interrelationships of the social and affective components of communication and their underpinnings, elements that are central to human experience. Insights from these studies will add unique knowledge to our understanding of social development as well as contribute to better-informed treatment methods in the future.
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0.922 |
2009 — 2010 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Basis of Sign Language From Lesion Mapping @ Salk Institute For Biological Studies
DESCRIPTION (provided by applicant): Sign language provides a means to understand the sensory-motor influences on the neural organization of language. The goals of the present proposal are to uncover the neural basis of sign language using modern lesion-deficit mapping. This will not only answer some fundamental questions about the neural basis of sign language and related processes and address questions about the sensory-motor forces that shape language organization generally, but will also provide much needed information on the clinical-anatomic correlates of sign language aphasia. We propose three specific aims. Aim 1: To determine whether the overall lesion pattern associated with sign language aphasia is similar to that found for spoken language using quantitative lesion-symptom mapping methods. Aim 2: To map the lesion pattern associated with more fine-grained measures of sign language production, sign language comprehension, and related function using quantitative lesion-symptom mapping methods. Aim 3: To assess the neural basis of naming ability and working memory for signs using the lesion method. PUBLIC HEALTH RELEVANCE: An important aspect of the mission of NIDCD is research that leads to increased understanding and treatment of language and communication disorders, particularly with respect to deafness and sign language. Relatively little research has targeted the breakdown of sign language as a result of brain lesions until our previous studies;the program proposed here using modern lesion-symptom approaches provides important new tools for the understanding and treatment of language disorders in deaf signers. This will have implications across a wide range of public health domains and directly benefits clinicians, educators, and individuals caring for deaf signers with brain lesions and/or language disorders.
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1 |
2011 — 2015 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Project 5: Characterization of Social Phenotype @ Salk Institute For Biological Studies
One of the most compelling features of Williams syndrome (WS) is the distinctive social profile that holds promise for understanding the underlying neurogenetic systems that provide meaning to human social interaction. Our studies to date suggest that while individuals with WS typically demonstrate an increased appetitive social drive, the social profile is characterized by dissociations (e.g., overly-friendly with a difficulty in making friends; socially fearless but anxious; positive affect with maladaptive behaviors). The aims of Project V focus on the characterization of the social phenotype of WS, enabling links to the genetic and neurobiological pathways of these dissociations. To this end, the Specific Aims are: Aim 1: Insatiable Appetitive Drive for Approaching Strangers will examine the underpinnings and variability of the increased attraction and approachability towards unfamiliar people observed in individuals with WS. Aim 2: The Unique Salience of Faces will elucidate the nature and underlying mechanisms of the atypically high interest in faces in WS, and its relation to the resultant hypersocial phenotype. Aim 3: Unusual Emotional Sensitivity will investigate both (a) the perception and processing of affect of others by those with WS, and (b) the overall affective style of individuals with WS. Using a multi-method design reflecting multiple levels of explanation (electrophysiology, autonomic function, and eye fixation). Project V studies will produce highly nuanced, quantifiable and independent key dimensions of the unique social behavior characteristic of WS. From a theoretical standpoint, a major thrust of the proposed work is to disentangle the processing of key components of social interaction and their respective underpinnings in the context of the enigmatic, yet paradoxical, WS social phenotype, with the ultimate goal of characterizing the complete system of social behavior and understanding the ways it can break down. Such a multileveled approach has not been previously adopted within this domain of inquiry. Results from these studies will add unique knowledge to our understanding of social behavior, by further defining the pathways implicated in gene-brain-behavior linkages, and are designed to contribute to better-informed treatments.
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1 |
2011 — 2015 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core B: Subject Recruitment, Diagnostic Testing, and Data Centralization Core @ Salk Institute For Biological Studies
The PPG is committed to a tightly integrated, cross-disciplinary design, bringing multiple levels of analysis and techniques to bear on shared specific themes in linking social phenotype to brain to gene. An overarching goal for the PPG is to create a framework to link each Project with the others. Core B is at the heart of this function, ensuring that, to the extent possible, participants are investigated by each of the disciplines represented by the different Projects. Core B, based at The Salk Institute's Laboratory for Cognitive Neuroscience (LCN), with Dr. Ursula Bellugi serving as Principal Investigator, is an efficient model for achieving this goal through its provision of a central infrastructure for the following services: (i)Planning and executing outreach activities that establish and maintain connections with the target participant communities (WS, DD) through referral sources as well as local, national, and international organizations;(ii)ldentifying and recruiting potential participants;(iii) Performing the induction screening, administering and scoring the Core Diagnostic Battery, and gathering medical and background information necessary for the application of inclusionary/exclusionary criteria;(iv) Administering and scoring a Core Cognitive Battery;(v) Coordinating an efficient schedule of participation across Projects;(vi) Tracking and ensuring the participation of all subjects across Projects;(vii) Coordinating the acquisition, transport, and collection of human tissue samples (e.g., blood samples for Project I;dental pulp for Project 11;brain tissue for Project 111). Overall, Core B centralizes the participant recruitment efforts and oversees participant tracking and participation inappropriate Projects.
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1 |
2011 — 2015 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core a: Administrative, Intergration and Neurocomputational Approaches Core @ Salk Institute For Biological Studies
The overarching goal of Core A is to provide the basic Adnninistrative, Data Centralization and Management, and Statistical Services/Data Integration required by all projects to: (i) Provide unified administrative services; (ii) Facilitate scientific and administrative communication; (iii) Manage the central data archives and facilitate exchange of verified data; (iv) Coordinate statistical services consultation for the participating investigators; and (v) Apply bioinformatics / neurocomputational approaches to integrate our multimodal data, from the molecular genetic level to that of social behavior. To this end, the Objectives are: (a) Administrative Services Fostering Interactivity and Integration, to coordinate daily functioning of a complex interdisciplinary research enterprise by coordinating communications and scientific activity among the Projects and Cores, providing budgetary planning and control, and facilitating and promoting collaboration and interactivity among investigators and consultants; (b) Data Centralization and Management, Data Quality Control, Core Statistical Services, and Multidimensional Data Integration, to maintain a secure, centralized, and immediately sharable database in order to facilitate collaboration and integration, to provide basic statistical consulting services, and to coordinate data integration by applying bioinformatics / neurocomputational approaches to our large database to reveal cross-level associations. The vitally important functions of Core A thus help to manage and integrate data from different domains with the ultimate goal of characterizing the system of human social behavior against the backdrop ofthe WS social phenotype. The testimony of the enormous success of Core A function as an Administrative and Data Centralization and Integration Core is our highly impressive list of interdisciplinary publications stemming from the decade of this Program Project. RELEVANCE (See instructions): Our goal is to integrate the gene, neural systems and behavioral project findings to forward our understanding of Williams syndrome. This study may help identify educational, social and medical-health support approaches appropriate for WS. The new bioinformatics and computer modeling techniques developed for this study will also be applicable to other multi-level brain research studies.
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1 |
2011 — 2013 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Williams Syndrome: a Model For Linking Genes, Neural Systems and Social Phenotype @ Salk Institute For Biological Studies
DESCRIPTION [Provided by Applicant): The overarching goal of this application is to link social-affective functions to their underlying neurobiological and molecular genetic bases, using Williams syndrome (WS) as a model. The theme leads from the investigators' past studies to the hypothesis that genetic and neuropeptide dysregulation underlies the social-affective features of WS. They continue to employ a multi-pronged approach incorporating new techniques and approaches to understanding the neurogenetic systems involved in the WS social phenotype. To this end, Project I: Gene Networks for Social Cognition, will determine the role of WS genes in social-emotional behavior using individuals with both full and atypical deletions; the role of genetic variations for neurotransmitters and neuropeptides in WS social-emotional behavior; the expression of WS and neuropeptide receptor genes in WS brain; and the genetic transcriptional networks altered in WS. Project II: Modeling WS using Human Neurons, will model typical and affected human nervous system development in WS using pluripotent stem cells. Studies will target genes implicated in social behavior within the WS region. Project III: Cellular Architectonics and Local Circuits, will examine the structures implicated in the social brain in WS on a unique collection of WS brains. Project IV: Neuroimaging of Social Circuitry, will utilize new multimodal, integrated structural and functional neuroimaging techniques to test hypotheses about the relationships among brain anatomy, physiology, cognition, and genetics in WS. Project V: Characterization of the Social Phenotype of WS, will characterize three independent key dimensions of altered social-affective behavior WS, including the pathways of several dissociations, incorporating new technologies and probes for behavior, psychophysiology, and electrophysiology. Genetic concepts have been used to map out the program project, and will be integrated at the level of the organism (Projects IV and V), brain/gene expression (Project III), and cell (Project II), to parse genes and transcriptional networks underlying social behavior. Results have the potential to move our understanding forward in unprecedented ways, providing a critical contribution to Social Neuroscience. RELEVANCE: A mission of NICHD includes research that leads to increased understanding and treatment of social behavior and emotional disorders. The investigators propose research that targets the study of genes, neural circuits, and social behavior in new and innovative ways, the results of the studies will provide unprecedented integration of the genetic and brain processes responsible for human social behavior, and key to novel treatments.
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1 |
2012 — 2013 |
Bellugi, Ursula |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Project 3: Cellular Architectonics and Local Circuits @ Salk Institute For Biological Studies
PROJECT III ABSTRACT Wlliams Syndrome is a rare neurodevelopmental disorder with a characteristic behavioral profile that includes an abundance of affectivity or hypersociability. Neuroimaging findings from Project IV indicate that the atypical affiliative behavior in WS is related to enhanced development of anterior regions including parts of the frontal lobe and the temporal lobe. However, no anatomical information is currently available at the microstructural level for any parts of the social brain circuitry in WS. Project 111 aims to identify the fundamental microstructural differences that account for the observed augmentation of the social brain in WS, including whether numbers of neurons, degree of arborization or distribution of specific neuronal subpopulations constitute the factors underlying the observed changes in the frontal lobe and the amygdala. Specifically, we will investigate: (1) the differences in the neuronal number and cell body size that contribute to observed changes in density, (2) the differences in connectivity inferred by cellular arrangement of neurons within cortical layers and (3) expressed by degree of arborizations and morphology of neurons, (4)differences in distribution of elemental factors associated with synaptic activity and cellular metabolism. Using a combination of well established techniques including stereology and the Golgi method, we will address fundamental questions of the microarchitecture in WS social brain regions. In additional, we employ a groundbreaking technique of synchrotron-based x-ray fluorescence imaging to explore the possibility of altered distribution of specific neuronal subpopulations in WS as compared to TD. Our findings will provide a crifical neuroanatomical foundation to this Program Project and are essential components to integrating across biological scales and forming our comprehensive picture of the WS social phenotype.
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1 |
2012 — 2016 |
Bellugi, Ursula |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Basis of Gestural Communication: Evidence From Sign Language @ Salk Institute For Biological Studies
DESCRIPTION (provided by applicant): The overall aim of this project is to map the. The neural basis of gesture processing has received a great deal of attention in the last several years, particularly in connection with the mirror neuron theory of action understanding. This theory states that gestures are understood via motor simulation in the observer. Sign language provides a unique perspective on this issue given its extremely rich gestural system, its easy accessibility (as opposed to speech gestures which are largely obscured from view), and the opportunity to compare linguistic and non-linguistic forms of gestural processing. Sign language bridges the gap between the visuo-manual studies in animal models where mirror neurons were discovered and human language, where there is a tremendous concentration of research on the mirror system. There is substantial clinical importance as well, as the mirror system has been implicated in a range of acquired and developmental disorders ranging from apraxia and aphasia to autism. If therapies are being developed based on a motor simulation model of understanding, it is critical to have information regarding the validity of these claims. Sign language provides an ideal testing ground. In terms of theory, a dorsal-ventral model of gestural processing guides our investigations. Thus, the proposed project builds on a decades-long program of investigation into the neural basis of sign language and has four specific aims. Aim 1: Map of basic language functions in deaf signers using large-scale lesion-deficit mapping. Aim 2: Map the relation between perception and production of meaningless gestures using lesion and fMRI approaches. Aim 3: Map the relation between recognition and production of meaningful action and object-related gestures using lesion and fMRI approaches. Aim 4: Map the relation between recognition and production of pantomime vs. signed gestures using lesion and fMRI approaches.
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