Structural and Functional neural correlates of early postnatal deprivation

描述（由申请人提供）：尽管早期产后剥夺（ESD）与神经心理问题之间存在联系，但很少有研究调查有此类病史的儿童中被认为支持此类功能的神经基质是否异常。研究ESD神经系统后果的一小部分工作报告了功能性和结构性脑异常（Eluvathingal等，2006）。拟议研究的总体目标是利用成像技术探讨ESD的结构和功能神经生物学后果。我们将利用体积MRI、弥散张量成像（DTI）和-[11 C]甲基- l-色氨酸（AMT） PET来评估有ESD病史的儿童大脑皮层和皮层下区域以及白质通路的结构和功能完整性，并将这些发现与已报道的神经心理功能受损联系起来。首席研究员（PI）是一名临床心理学家，在脑-行为关系研究中具有设计和开展神经心理学表型研究的经验，他将作为培训计划的一部分，指导项目的所有阶段，包括神经科学、PET和MRI成像方面的教学培训，并与五位国际知名导师建立关系。在利用结构和功能成像工具调查大脑行为关系的研究中具有丰富的专业知识。培训协议的主要目的是为PI提供必要的工具，以获得对成像技术作为研究大脑行为关系的研究工具的基础机制的更深层次的概念理解，并在神经科学研究中利用成像协议/数据。提出的研究是第一批评估儿童ESD的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，将为暴露于ESD的儿童提供新的重要数据。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，并将发展成为一名独立的研究者。

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.