At least 60% of children treated for medulloblastoma with contemporary multimodality therapy (i.e., surgical resection, radiation therapy, and high-dose chemotherapy) will live more than 5 years after initial diagnosis. Unfortunately, the majority of these survivors ultimately experience IQ loss, learning difficulties, and academic failure. The long-term goal of our research is to identify neural substrates of cognitive deficits among long-term survivors of childhood cancer. The focus of this application is deficits in reading ability. The study is designed to test the hypothesis that behavioral deficits in reading decoding among medulloblastoma survivors reflect therapy-induced disruption of ventral visual processing during the development of reading skills. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) will be used in a longitudinal study to compare neural systems for orthographic processing in patients and age-similar controls. The neuroimaging data (fMRI and DTI) will be analyzed in relation to behavioral performance on a comprehensive battery of neuropsychological tests. This research will generate important insights into the fundamental causes of cognitive deficits associated with medulloblastoma therapy, identify potential targets for pharmacological and behavioral interventions to improve cognitive function in survivors who have already been treated, and discover opportunities to reduce the negative impact of medulloblastoma therapy on patients treated in the future. Furthermore, the medulloblastoma survivors will serve as a model population with acquired dyslexia related to well-defined therapeutic insult. The longitudinal behavioral and imaging studies in patients and healthy controls may yield new insights into the role of the ventral visual system in development of normal and abnormal reading ability in otherwise healthy children. ? ? ?
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