Natacha Akshoomoff - US grants

DESCRIPTION (provided by applicant): The clinical complexities of proper diagnosis and assessment of children with ASD, together with federal and state mandates to provide services, present significant challenges to local schools and public service providers. Autism is increasingly conceptualized to encompass a spectrum of disorders rather than a unitary, classically defined developmental disorder. Given the large number of behaviors that define the "autistic spectrum disorders" (ASD) and the variability seen across individual children even within the same diagnostic category, proper identification and assessment requires experienced clinicians and educators. It appears that better identification and broader categorization have contributed to the increasing numbers of children who are being identified with ASD. Standardized diagnostic instruments that have been demonstrated to be reliable and valid are now widely used in ASD research. While comprehensive, valid assessments are essential for educational planning, the direct clinical or educational benefits of diagnostic distinctions within the autism spectrum are a matter of debate. The applicant proposes to evaluate the range of diagnostic distinctions that are present in children who are receiving educational interventions under the autism category. The nature of diagnostic and educational assessments used by service delivery systems for children with autism will be investigated. These data will be used to determine how the broader definition of autism used by schools compares with a diagnosis based on the use of research-based standardized test instruments by experienced professionals. The applicant is requesting a Career Development Award (K23) to obtain the advanced training in services research she needs to address these issues. The applicant's strong background of academic, research, and clinical training in diagnostic and neuropsychological assessment in children, research design and statistics, and autism specific issues will provide an excellent foundation for this work. The proposed training goals, including becoming familiar with statistics and longitudinal techniques used in services research, and obtaining greater knowledge about schools and school-based assessment services, in conjunction with the research plan, will allow the applicant to pursue innovative approaches to implementing research-based diagnostic and assessment methods for children with autism in community settings.

DESCRIPTION (provided by applicant): Very preterm children are at high risk for neurodevelopmental impairments. Academic achievement and educational outcomes are significantly lower than expected, particularly in the area of mathematics. Even children with relatively benign neonatal courses who are deemed normal at infant/toddler follow-up remain at risk for significant math difficulties. In addition, these healthy preterm children are at risk fr significant attention, visual, perceptual, motor, and executive function deficits, but little is knwn about how the emergence of these deficits in preterm preschoolers may be related to later math difficulties. There are currently no data examining the neural basis of selective neuropsychological deficits and early academic difficulties, yet this is a critical period of dynamc neurocognitive development when intervention may have the best potential for mitigating later deficits. This longitudinal study aims to evaluate the emergence of neuropsychological and math deficits in healthy preterm children, map the impact of preterm birth on brain development during early childhood, and examine the relationship between math and neuropsychological development and developmental brain abnormalities in healthy preterm children. Participants will be 60 healthy preterm children (born 25-32 gestational weeks) with average intelligence and 40 full term children matched for age, sex, SES, and verbal IQ. Children will enter the study within 6 months prior to kindergarten entry. We will integrate multimodal neuroimaging (whole brain morphometric measures using structural MRI and indices of white matter integrity using diffusion weighted imaging) with neuropsychological and academic measures across three annual time points. We predict that specific early perceptual and cognitive deficits will be relate to emerging math deficits. We will examine whether later math deficits are related to early non-symbolic and symbolic processing deficits. Our longitudinal study design aims to elucidate the links between the most affected cortical surface areas and underlying fiber tracts and level of performance on a set of implicated neurocognitive and math functions, and to acquire more information about how these effects impact ongoing biological development in neural systems less directly affected early in development. We will also examine other mediating factors, such as degree of prematurity and medical and demographic variables. The results from this project will greatly enhance our understanding of why certain skills appear more vulnerable to preterm birth, how these skills are related to the early emergence of math deficits, and how the underlying neuropathology accounts for extensive variations in neurodevelopmental outcome in healthy preterm children. These results will provide the critical foundation for identifying the deficits most amenable to effective interventions.

DESCRIPTION (provided by applicant): This three-year project will leverage a unique, recently collected set of data entitled Pediatric Imaging, Neurocognition, and Genetics (PING), which includes neuroimaging, cognitive, demographic, behavioral, and genome-wide genotyping data for over 1,200 children and adolescents ranging from 3 to 20 years of age. This is the largest source of neuroimaging, genomics, and cognitive data across the developmental age span assembled to date and was created as a resource to the scientific community. We will conduct the first comprehensive and well-powered study of cognitive development and state-of-the-art neural architectural phenotypes and genome-wide genotyping in a large typically developing pediatric sample to advance the understanding of the neurobehavioral development of executive functions. Our preliminary studies have demonstrated that the measures of brain morphology, diffusivity, and signal intensity show varying contributions to the prediction of developmental phase at different ages in this sample, reflecting a dynamic cascade of biological changes within different tissue types. Results from the NIH Toolbox Cognitive Battery show that these measures are sensitive to neurodevelopmental effects and provide rich information about a variety of important cognitive functions. Our research project has four Specific Aims designed to link individual variability in executive function performance to typically developing neural systems and genetic influences, using cutting-edge nonlinear multidimensional statistical modeling and a novel polygenic risk scores approach for assessing aggregate genetic influence. We predict that these results will enhance our understanding of how cognitive dimensions change and emerge with changing neural phenotypes, and the impact of individual sociodemographic variation. This is critical to understanding variability in behavioral and neuropsychiatric outcomes and developing important prevention and intervention efforts.