Scientific Abstract from:
Nancy Minshew, M.D.
University of Pittsburgh
(In conjunction with Carnegie Mellon University and University of Illinois at Chicago)
Neurobiologic and Cognitive Mechanisms of Autism
The central theme of this program is that autism is a disorder of information processing 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-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 common measures 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.
Project I: Categorization & the abstraction of concepts in individuals with autism
Principal Investigator: Nancy J. Minshew
Co- Investigator: Mark Strauss
One of the most basic and important cognitive processes demonstrated by children and adults is the ability to form categories. This ability begins to develop in the first year of life even before language. Categorization allows us to identify novel objects and instances, reduce memory demands, and improve our memories for specific instances. More generally, it allows us to conceptually organize or make sense of our experiences and the world around us. In the first year of life it enables us to differentiate between male and female faces and identify basic objects before learning verbal labels. Studies from the first five years of the grant demonstrate prominent deficits in concept abstraction that account for the need to train young autistic children with mass trials to recognize concepts which when learned are not generalized or are applied rigidly without the capacity to consider context. This has implications for several key social abilities including the identification and memory of both objects, and the recognition of faces and facial affect. The goal of Project I is to study the category abstraction abilities of both autistic individuals and family members of diagnosed autistics. The studies will focus on two domains of knowledge - faces and objects. The studies with faces will explore both the categorization of facial information (gender and expression) and the ability of participants to form prototypical representations and use this information for facial recognition. It is expected that well know deficits among autistic individual in their abilities to perceive and remember faces will be explained by these studies. A related set of studies will focus on the object categories. It is hypothesized that autistics do not form categories in which exemplars differ in typicality and that they do not form prototypic representations of object categories. We will also investigate the familiality of these deficits to determine if they can be used as endophenotypic markers that more accurately mark affectation than currently used phenotype markers. These proposed deficits may be the result of aberrant processes related to the fusiform gyrus, a possibility that will be explored more directly by comparing the results of this project with those of Project II.
Project II: Disordered visual processing in autism: Developmental, behavioral, & Neural investigations
Principal Investigator: Marlene Behrmann
Co- Investigators: Nancy J. Minshew and Beatriz Luna
No description is available at this time.
Project III: Sensory, motor, & executive deficits in autism: Oculomotor, psychophysical, & fMRI studies
Principal Investigator: John A. Sweeney
Co- Investigator: Beatriz Luna
Autism remains a poorly understood neurodevelopmental disorder for which the underlying brain substrates and genetic causes remain unspecified. In Project III, the tools of clinical cognitive neuroscience and functional brain imaging will be used to systematically address fundamental questions about cognitive, neurobiological, neurodevelopmental and genetic aspects of autism. 160 high functioning autistic individuals (half with a history of early language delay and half without) will be matched with 160 healthy subjects. Half of each group will be between 8 and 16 years of age with the remainder between 17 and 45 years. All subjects will participate in laboratory studies of sensorimotor aspects of eye movement control, studies of executive cognitive skills subserved by prefrontal systems, and psychophysical studies of auditory and visual sensory abilities. Ninety subjects in each group will participate in fMRI studies (30 subjects per group per study) that will individually address three separate domains of deficit: 1) visual motion processing and the use of visual motion information for pursuit eye movements, 2) lateralized abnormalities in brain function using finger tapping, visually guided saccades, and sensory processing of monaural auditory stimuli and visual motion information presented separately to each hemifield, and 3) executive cognitive processes of working memory and voluntary response suppression. Following up on preliminary data suggesting greater deficits in basic eye movement control in autistic individuals without language delay and greater executive cognitive deficits in those with language delay, differences between these groups of autistic individuals will be examined aiming to define subgroups of individuals within the autistic spectrum that could be useful for neurobiological and genetic research. Age-related differences between autistic and healthy subjects in their developmental profiles for acquiring sensory, motor and cognitive skills through late childhood and adolescence will be examined. Fifty families with an autistic proband will be included in laboratory studies to determine whether sensory, motor and cognitive deficits seen in autism are present in family members.
Project IV: Brain activation & functional connectivity in cognition
Principal Investigator: Marcel Just
Co- Investigator: Robert Siegler
No description is available at this time.