Structural and Functional neural correlates of early postnatal deprivation

描述(申请人提供)：尽管早期产后剥夺(ESD)和神经心理问题之间存在联系，但很少有研究调查有这种病史的儿童中被认为有助于辅助这种功能的神经底物是否异常。研究ESD的神经学后果的一小部分工作报告了大脑的功能和结构异常(Eluvathingal等人，2006年)。拟议研究的首要目标是用成像技术探索ESD的结构和功能神经生物学后果。我们将利用体积磁共振、弥散张量成像和a-[11 C]甲基-L-色氨酸(AMT)PET来评估有ESD病史的儿童皮质和皮质下脑区和白质通路的结构和功能的完整性，并将所发现的结果与有ESD病史的神经心理功能受损联系起来。首席调查员(PI)是一名临床心理学家，在设计和实施在大脑-行为关系调查中定义神经心理表型方面的研究方面具有丰富的经验，他将作为培训计划的一部分，领导该项目的所有阶段，该培训计划包括神经科学、PET和MRI成像方面的授课培训，以及与五名国际知名导师的关系，这些导师都拥有利用结构和功能成像工具进行大脑-行为关系研究的丰富专业知识。培训方案的主要内容包括为PI提供必要的工具，以更深入地从概念上理解成像技术作为研究大脑-行为关系的研究工具的机制，并在神经科学研究中利用成像方案/数据。这项拟议的研究是第一批评估儿童ESD的神经解剖学相关性的研究之一。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。神经影像数据可以用来监测治疗干预的效果，并评估发现的潜在可逆性，这在过去是不可能的。因此，这些研究具有潜在的翻译价值。从申请者的角度来看，拟议的学习是勾勒出的职业目标的重要组成部分，因为申请者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调查人员。

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.