Development of Neural Systems Underlying Learning and Response to Novelty

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This is a revised K01 proposal designed to foster expertise in the application of neuroimaging to a developmental investigation of learning based on environmental statistics, namely frequency and association-based learning. The candidate has formulated a detailed career development plan composed of didactic coursework, neuroimaging workshops, and ongoing supervision, training, and consultation with field experts. The proposed training will be conducted at the Sackler Institute at the Weill Medical College of Cornell University. The Sackler houses several world-renowned cognitive developmental neuroscientists and is one of the few facilities dedicated entirely to developmental research using neuroimaging technology. In previous work, we found the striatum to be involved in simple frequency-based learning and the hippocampus to be involved in associative learning. We will test the hypothesis that while these forms of learning are intact early in development, the ability to efficiently maintain information during learning and adjust behavior when learned information is violated by novel information develops more gradually as the underlying neural circuitry (e.g., frontostriatal and frontohippocampal circuits) is organized. Statistical manipulations in the frequency with which stimuli are presented and/or associated with other stimuli will be the primary manipulation. Saccade latency in infants, and both saccade latency and reaction times in children, adolescents, and adults will be used as behavioral dependent measures. In a separate session, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)will be used with the same children, adolescents, and adults to assess changes in the recruitment of brain areas and in connectivity between these areas as a function of learning and development. These studies have significant implications for children born preterm and very low birth weight (VLBW, < 1500 grams) who are highly susceptible to subtle striatal and hippocampal injury in the perinatal period, and approximately 40% of who will have some learning disability. By tracking changes in the learning functions of this circuitry across typical development, these studies will lay the foundation for clinical studies that can identify precise learning disruption (specific to striatal or hippocampal circuitry) and associated outcomes and learning disabilities in this preterm and VLBW population. The K01 studies will provide a means by which interpretations of data from future clinical studies can be constrained.