Structural and Functional neural correlates of early postnatal deprivation

描述（由申请人提供）：尽管出生后早期剥夺（ESD）和神经心理问题之间存在联系，但很少有研究调查被认为有助于这些功能的神经基质在有此类病史的儿童中是否异常。研究ESD中神经学后果的小部分工作报告了功能性和结构性脑异常（Eluvathingal等人，2006年）。拟议的研究的总体目标是探索，与成像技术，结构和功能的神经生物学后果的ESD。我们将利用容积MRI、弥散张量成像（DTI）和α-[11 C]甲基-L-色氨酸（AMT）PET来评价皮质和皮质下脑区以及白色物质通路的结构和功能完整性，并将结果与据报道有ESD病史的儿童受损的神经心理功能联系起来。主要研究者（PI）是一名临床心理学家，在设计和开展研究以定义大脑行为关系的神经心理学表型方面具有丰富经验，将作为培训计划的一部分进行项目的所有阶段，包括神经科学和PET和MRI成像的教学培训，以及与五位国际知名导师的关系，他们都在利用结构和功能成像工具调查大脑行为关系的研究方面具有丰富的专业知识。培训方案的主要目的是为PI提供必要的工具，以获得对成像技术作为研究脑行为关系的研究工具的机制的更深入的概念性理解，并在神经科学研究中利用成像方案/数据。拟议的研究是第一个评估人类儿童ESD神经解剖学相关性的研究。我们将MRI和PET方法与神经心理学评估相结合的方法是创新的，将产生关于暴露于ESD的儿童的新的重要数据。神经影像学数据可用于监测治疗干预的效果，并评估结果的潜在可逆性，这在过去是不可能的。因此，这些研究具有潜在的翻译价值。从申请人的角度来看，拟议的研究是概述的职业目标的重要组成部分，因为申请人将从既定的导师和共同导师那里学习MRI和PET成像技术，并将发展成为独立的研究者。

DESCRIPTION (provided by applicant): 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.