| 1987 — 1988 |
Minshew, Nancy J |
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. |
Developmental Neurobiology of Infantile Autism @ University of Pittsburgh At Pittsburgh
early infantile autism; developmental neurobiology;
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| 1990 — 1993 |
Minshew, Nancy J |
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. |
Psychobiology of Autism @ University of Pittsburgh At Pittsburgh
Over the years, various theories have been advanced to account for the clinical manifestations of autism. These theories have each proposed a localization for the neuropathology within the neuraxis as well as a theory about the nature of the pathophysiology. Overall, these theories have postulated pathology at three different levels within the neuraxis-- the cerebral cortex, the limbic system, and the posterior fossa. The purpose of this project is to examine evidence for the three competing brain localizations hypothesized in autism-- the cerebral cortex, the limbic system and the posterior fossa. A related purpose is to provide evidence, where possible, which will evaluate different theories at the same localization, e.g., the association cortex theory, the auditory processing theory and the selective attention theory of the cerebral cortex, and the brainstem theory and the cerebellar theory. These goals will be pursued with selected neuropsychologic, oculovestibular, and magnetic resonance imaging measurements. The results of this proposed study will be compared with the brain neurochemistry results from the investigators' study of in vivo 31p NMR spectroscopy study in autism. The subjects for this study will be 60 non-mentally retarded autistic individuals and 60 age, IQ, sex and race matched normal controls who will be recruited over four years. When added to the subjects from the initial two year study, this will result in a cohort of 90 autistic individuals and 90 matched controls by the end of this study, with 30 autistics and 30 controls in each of three age groups-- children, adolescents, and young adults. All subjects will be studied at entry and the children and adolescents from the initial two year study and the first year of this study will be reevaluated at the end of three years.
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| 1994 — 2000 |
Minshew, Nancy J |
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. R55Activity Code Description:
Undocumented code - click on the grant title for more information. |
Cortex and Complex Information Processing in Autism @ University of Pittsburgh At Pittsburgh
DESCRIPTION (Investigator's Abstract): Autism is a fascinating disorder of complex cognitive abilities and behavior which may ultimately prove to be the consequence of an abnormality in neural connectivity at the systems level. Neurobiologic research in the past 10 years has substantially redefined the neurobiologic characterization of autism, with the predominance of evidence now pointing to dysfunction of cerebral cortex. Based on our research findings to date, our worKing hypotheses propose that the selective pattern of cognitive deficits in autism is secondary to a generalized deficit in complex information processing and is characterized by a dissociation between complex tasks and more basic abilities across domains and modalities. We further hypothesize that these deficits are the consequence of a generalized abnormality in the development of the local and distant connections of association cortex. The goal of this proposal is to investigate the structural and functional evidence for the role of the cerebral cortex in the pathophysiology of autism. This goal will be accomplished through the study of 100 carefully diagnosed and screened high functioning autistic individuals aged 8-30 years and 100 normal controls individually matched on age, IQ, gender, and race and group matched on SES of the family of origin. These subjects will have: 1) a battery of neuropsychologic and language tests designed to demonstrate the distinctive pattern of cognitive deficits and abilities in autism; 2) studies of cortically controlled eye movements to investigate the physiology and circuitry of the cerebral cortex; 3) quantitative morphometries of the brain with volumetric MR imaging to provide measurements of unimodal and heteromodal association cortex, white matter, and corpus callosum, as well as limbic and posterior fossa structures relevant to pertinent negative hypotheses; and 4) 31P and `H MRS to investigate the molecular metabolic neuropathology autism by assessing the phospholipid metabolism of brain membranes and neuronal cell number respectively, and thus providing a potential independent measure of the underlying pathophysiology in autism. The data from these studies will be used in various binations in correlational analyses to test the hypotheses of this study. These analyses will include pertinent positive tests of our hypotheses as well as tests of pertinent negative tests.
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| 1997 — 2006 |
Minshew, Nancy J |
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. U19Activity Code Description:
To support a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach. A cooperative agreement research program generally involves the organized efforts of large groups, members of which are conducting research projects designed to elucidate the various aspects of a specific objective. Substantial Federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of award. The investigators have primary authorities and responsibilities to define research objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations and conclusions of their studies. Each research project is usually under the leadership of an established investigator in an area representing his/her special interest and competencies. Each project supported through this mechanism should contribute to or be directly related to the common theme of the total research effort. The award can provide support for certain basic shared resources, including clinical components, which facilitate the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence. |
Neurobiologic and Cognitive Mechanisms of Autism @ University of Pittsburgh At Pittsburgh
DESCRIPTION (provided by applicant): The central theme of this program is that autism is a disorder that disproportionately impacts complex information processing and results from abnormal development of integrative circuitry in neural systems and specialization of local circuitry in neocortex. This is exhibited in deficient higher order cognitive processes, reduced fMRI activation of executive and semantic processing regions during complex information processing, and a local processing approach to cognitive tasks. Project I will focus on concept abstraction as it applies to object categories, face recognition (gender and identity) and facial affect recognition. Project II will investigate the perceptual competence of the ventral visual stream and its development using microgenetic analysis to examine the behavioral and neural mechanisms mediating face and object recognition and the capacity of subjects to derive configurations from local elements. Project III will investigate disturbances in oculomotor control, sensory hyperacuities, lateralized disturbances of brain function, and the developmental acquisition of executive cognitive functions in childhood and adolescence. Project IV will investigate brain connectivity by evaluating the synchronization of activity across brain regions involved in language comprehension tasks, and the development of reasoning and problem solving abilities. In addition to laboratory studies, Projects II to IV will use MRI to evaluate disturbances in brain maturation and functional cortical integration. The Administrative Core will provide administrative, fiscal, and scientific oversight for the program project and a nidus for scientific interactions and training of junior scientists. It will also support our participation in network governance and cross-site studies. The Subject & Genetics Core will recruit the subjects for the projects, complete the network and other measures as needed for network studies, and conduct the CPEA Network Genetics studies. The Statistical Analysis and Image Processing Core will provide statistical support to the projects and continue statistical research on methods for improving the processing and analysis of fMRI data.
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| 2007 |
Minshew, Nancy J |
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. |
Administrative, Data Management and Statistical Core @ University of Pittsburgh At Pittsburgh |
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| 2007 — 2011 |
Minshew, Nancy J |
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. |
Biological and Information Processing Mechanisms Underlying Autism @ University of Pittsburgh At Pittsburgh
This center focuses on elucidating fundamental information processing and neurobiological mechanisms causing autism. It incorporates 5 themes: 1) autism as a disorder of complex information processing abilities WITH intact or enhanced basic abilities;2) autism as a disturbance in cerebral connectivity with under connectivity of long-distance connections and over-connectivity of compensatory local connections;3) autism as a developmental disorder whose brain-behavioral manifestations change with each stage of brain maturation from childhood to adulthood;4) that the pathognomonic social impairments are best understood in terms of underlying information processing mechanisms;and 5) that emotional and affective impairments are a major component of the syndrome and significant contributor to impaired function and serious behavior issues. These goals will be addressed using behavioral, cognitive, fMRI, DTI, DTT, and neuropathologic studies of: infant siblings, first-diagnosed toddlers with autism, and groups of children, adolescents, and adults with and without autism. Project I: Development of Categorization &Facial Knowledge in Low &High Functioning Autism;Project II: Disturbances of Affective Contact: Development of Brain Mechanisms for Emotion Processing;Project III: Systems Connectivity &Brain Activation: Imaging Studies of Language &Perception;Project IV: Diffusion Tensor MRI &Histopathology of Brain Microstructure &Fiber Pathways. Project I focuses on understanding the earliest manifestations of autism and the development of earlier diagnostic tools;it also focuses on information processing mechanisms underlying social and cognitive symptoms. Project II focuses on elucidating emotion processing mechanisms and the maturational disturbances from childhood through adulthood;these studies will clarify how individuals with autism experience, understand and regulate emotion, and will also examine their self-awareness of emotion. Genetic modifiers of emotionality will also be determined. Project III focuses on understanding disturbances in functional brain connectivity that underlie the impaired processing of information and in turn the cognitive and behavioral impairments in autism. The project also includes innovative machine-learning studies of how the brain identifies and categorizes words and computational modeling of cortical function. Project IV looks at structural connectivity of specific white matter pathways and the histopathology of intra-cortical white matter projections. This project will help reconcile the functional under-connectivity and early structural overgrowth in autism. The identification of fundamental information processing mechanisms underlying the behavior of autism will lead to the development of more specific and effective interventions;similarly identification of connectivity alterations can lead to targeted cognitive interventions that increase neural connectivity. This research addresses Autism Research Matrix goals # 1,2,3,6,16,17,19,22,23,26,31,and 34.
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| 2007 — 2011 |
Minshew, Nancy J |
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. |
Subject Assessment and Recruitment Core @ University of Pittsburgh At Pittsburgh
3 year old; Adolescent; Adult; Affect; Age; Age-Years; American Psychiatric Association; Attention; autism spectrum disorder; Autistic Disorder; base; behavior measurement; behavior test; Behavioral; biological information processing; Blood; Blood specimen; Body of uterus; Calendar; Child; Claustrophobias; Commit; Data; data acquisition; Databases; Development; Diagnosis; Diagnostic; Diagnostics Research; disability; Eligibility Determination; Environment; experience; Family; Family history of; Functional Magnetic Resonance Imaging; Genetic; Image; Indiana; Individual; Infant; Intake; Intellectual functioning disability; Intelligence; interest; Interview; Karyotype determination procedure; Kentucky; Language; Letters; Magnetic Resonance Imaging; Maryland; Measures; Medical; medical examination; meetings; member; mental age; Mental disorders; Mission; Montana; Motion; Movement; National Institute of Mental Health (U.S.); neuroimaging; Neurologic; neuropsychological; Neuropsychological Tests; New York; Newly Diagnosed; North Dakota; Ohio; Participant; Pennsylvania; Postdoctoral Fellow; Principal Investigator; Procedures; Process; programs; Psychology; Reading; Records; Recruitment Activity; repository; Research; Research Personnel; Research Project Grants; Sample Size; Sampling; Screening procedure; Siblings; Site; Source; South Dakota; success; System; Telephone; Test Result; Testing; Time; Training; Universities; West Virginia; Wyoming
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| 2009 — 2013 |
Minshew, Nancy J |
R21Activity Code Description:
To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) R33Activity Code Description:
The R33 award is to provide a second phase for the support for innovative exploratory and development research activities initiated under the R21 mechanism. Although only R21 awardees are generally eligible to apply for R33 support, specific program initiatives may establish eligibility criteria under which applications could be accepted from applicants demonstrating progress equivalent to that expected under R33. |
Adapting Cognitive Enhancement Therapy For Asd @ University of Pittsburgh At Pittsburgh
DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) are defined by specific behavioral impairments in social interactions, verbal and non-verbal (gaze, face expression, gestures, prosody) communication, imaginative play, and by restricted and repetitive interests and behavior. Underlying these behaviors are deficits in social and non- social cognition and information processing. Interventions for autism have largely focused on the preschool years and behavioral methods. Few interventions are available for adults with ASD, and even fewer focus on the remediation of cognitive and social-emotional deficits in a way designed to improve complex adaptive behavior essential for success and achievement in adult life. As a consequence, many verbal adults with ASD experience substantial lifetime disability resulting in great personal and family suffering and great financial cost. In response to RFA-MH-09-021, Novel Interventions for Neurodevelopmental Disorders, we propose the first step in adapting, piloting and preliminarily testing of the efficacy of Cognitive Enhancement Therapy (CET) for young transitional age high functioning adults with ASD to improve adaptive functioning and adult life achievement in this population. CET is a neurodevelopmentally-based, social-cognitive and neurocognitive rehabilitation program originally developed for schizophrenia that has demonstrated significant improvements in cognition and important functional outcomes. Many of the social, communication, and cognitive impairments experienced by persons with ASD (e.g., impaired theory of mind, deficient emotion perception, poor emotion regulation and expression, inflexibility, executive dysfunction) are also shared by individuals with schizophrenia. These impairments are directly targeted by CET, suggesting that CET may confer substantial benefits to verbal individuals with ASD who often do poorly as adults and for whom few interventions exist. This project will consist of two phases. In the first (R21) phase, adaptations to the CET treatment reflecting the uniqueness of autism will be made through the development of a supplement to the existing CET treatment manual. Clinical experts in autism and schizophrenia will collaborate to adapt CET, and then conduct an uncontrolled pilot study of these adaptations with 12 young adults with ASD to demonstrate feasibility, identify the need for additional adaptations, and provide an initial evaluation of the potential social-emotional and cognitive effects of the approach. In the second (R33) phase, a small-scale randomized trial with 55 young adults with ASD will be conducted to obtain initial efficacy data on a broad range of cognitive, functional, and neurobiological outcomes to support the feasibility of a larger and more definitive trial of CET for ASD. The proposed R21-R33 will result in the completion of the first rigorous clinical trial of a proven cognitive rehabilitation approach with verbal adults with ASD. If successful, this project will result in a major step forward in available interventions for adults with ASD, and have implications for both younger individuals with autism and other neurodevelopmental disorders that share similar cognitive, affective and social impairments.
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