Studies utilizing modern neuroimaging techniques have provided clear evidence that the adolescent brain is actively developing. This neurodevelopment, particularly in the frontal lobes, coincides with improvements in several areas of higher order cognitive functioning, including working memory abilities. It has been documented that working memory skills are crucial to the intact performance in several other cognitive domains. Deficits in working memory have been demonstrated among a number of neurological and psychiatric conditions that manifest during adolescence. However, the neurobiological substrates of working memory in even normally developing adolescents remain unclear. The current cross-sectional study proposes to integrate neuropsychological, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques to more clearly explore frontal lobe white matter development as it relates to both verbal and spatial working memory functioning in 90 typically developing adolescents (ages 12 to 17). It is hypothesized that 1) working memory abilities will be positively associated with age, 2) adolescents will show a hemispheric dissociation between the verbal and spatial working memory tasks that will become more pronounced with increasing age, 3) prefrontal white matter integrity will show a significant positive correlation with age and will mediate the positive relationship between age and working memory performance, and 4) prefrontal white matter integrity will be positively associated with nearby cortical fMRI response during the working memory tasks. The applicant is requesting a five-year mentored Career Development Award (K08) in order to develop the skills and expertise necessary for answering these research questions. Career development activities will include training in DTI data collection and analysis, development of expertise in fMRI, training in developmentally-focused longitudinal study design and analytical techniques and continued training in the ethical conduct of scientific research with children and adolescents. The proposed training plan will include structured coursework, seminars, and mentoring by experts in the fields of development and neuroimaging. Together, the implementation of this training and research plan will provide the beginnings of a much-needed framework for understanding the neurobiological substrates of working memory during adolescence and will allow the applicant to transition into an independent investigator specializing in longitudinal examination of adolescent cognition and neurodevelopment.
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