Despite links between early postnatal deprivation (ESD) and neuropsychological problems, few studies have investigated whether the neural substrates thought to subserve such functions are abnormal in children with such histories. The small body of work that has investigated neurologic consequences in ESD has reported both functional and structural brain abnormalities (Eluvathingal et al., 2006). The overarching aim of the proposed studies is to probe, with imaging techniques, the structural and functional neurobiological consequences of ESD. We will utilize volumetric MRI, diffusion tensor imaging (DTI), and a-[11 C]methyl-L- tryptophan (AMT) PET to evaluate the structural and functional integrity of cortical and subcortical brain regions and white matter pathways and link findings to the neuropsychological functions reported to be impaired in children with histories of ESD. The principal investigator (PI), a clinical psychologist with experience in designing and conducting research in defining neuropsychological phenotypes in investigations of brain-behavior relationships, will conduct all phases of the project as part of a training program that includes didactic training in neurosciences and PET and MRI imaging, and relationships with five internationally renowned mentors, all with substantial expertise in the conduct of research investigating brain-behavior relationships utilizing structural and functional imaging tools. The major thrust of the training protocols involve providing the PI with tools necessary to obtain a deeper conceptual understanding of the mechanisms that underlie imaging techniques as research tools for studying brain-behavior relationships, and in utilizing imaging protocols/data in neuroscientific research. The proposed studies are among the first to evaluate the neuroanatomical correlates of ESD in human children. Our approach of integrating MRI and PET methods with neuropsychological assessments is innovative and will yield new and important data on children exposed to ESD. Neuroimaging data can be used to monitor effects of therapeutic interventions and to assess the potential reversibility of findings, which has not been possible in the past. Thus, these studies have potential translational value. From the perspective of the applicant, the proposed studies are an important component of the outlined career goal in that the applicant will learn both MRI and PET imaging techniques from an established mentor and co-mentors and will develop into an independent investigator. ? ? ?
