Genetics, Neurobiology, and Cognition in Down Syndrome

该项目的主要目标是尽可能准确地确定唐氏综合症患者精神发育迟滞的神经基础。三个项目将探索功能障碍在海马体结构(HF)和前额叶皮质(PFC)中的作用。在第一个项目中，受试者分为两个年龄段(年轻：6-14岁。和老年人：30-40岁)将接受一系列神经心理学任务的测试，旨在评估这两个大脑区域的功能。这个项目的具体目的是描述DS患者一生中的神经认知障碍。在最小的年龄，这些知识将有助于制定有针对性的干预计划。在年龄最大的时候，这样的知识应该有助于识别这些人 有发展成早期阿尔茨海默病的风险。在第二个项目中，我们将结合 神经心理测试和神经成像方法，以更准确地确定HF和PFC的功能障碍程度。神经成像范式将允许我们将认知表现与大脑形态和大脑激活直接联系起来，从而确定在特定任务中表现不佳与结构和/或功能异常的程度。我们将使用高分辨率磁共振成像(MRI)进行结构研究，并使用功能MRI进行激活研究。在第三个项目中，我们将组成患有DS的高功能青少年和低功能青少年的不同小组，并使用相同的 神经心理学和神经影像学方法。我们在这里的目的是确定DS的低功能是否反映了目标大脑系统(如HF和PFC)的特定损害，或者它是否反映了非局部性大脑差异，如整体大脑大小。总体而言，这个项目旨在加深我们对DS神经认知表型的理解，这将在三个方面促进进展：(1)这些信息将有助于建立一个更准确的DS认知缺陷的小鼠模型；(2)这些信息将为那些在生命早期或以后制定干预策略的人提供指导，当阿尔茨海默病的风险显著时；以及(3)这些信息将阐明低功能和高功能个体之间的关键差异 从而为那些预后最差的个体提供帮助的策略。

The major objective of this project is to define as precisely as possible the neural underpinnings of the mental retardation observed in Down syndrome. Three projects will explore the role of dysfunction in the hippocampal formation (HF) and prefrontal cortex (PFC). In the first project, subjects in two age groups (young: 6-14 yrs. and old: 30-40 yrs) will be tested on a battery of neuropsychological tasks aimed at assessing the function of these two brain regions. The specific aim of this project is to characterize the neurocognitive impairment across the life-span in DS. At the earliest age such knowledge will help in the development of targeted intervention programs. At the oldest age such knowledge should help identify those individuals most at risk for the development of early Alzheimer's disease. In the second project we will combine neuropsychological tests and neuroimaging methods, to more precisely determine the extent of dysfunction in HF and PFC. The neuroimaging paradigms will allow us to directly relate cognitive performance to both brain morphology and brain activation, thereby determining the extent to which poor performance on particular tasks coincides with abnormal structure and/or function. We will use high-resolution magnetic resonance imaging (MRI) for the structural studies, and functional MRI for the activation studies. In the third project we will constitute separate groups of high- and low-functioning adolescents with DS, and employ the same battery of neuropsychological and neuroimaging methods. Our purpose here is to determine whether low functionality in DS reflects specific impairments in target brain systems such as HF and PFC, or if it reflects non-localized brain differences, such as overall brain size. Overall, this project aims to sharpen our understanding of the neurocognitive phenotype in DS, which will foster progress in three areas: (1) this information will help create a more exact mouse model of the cognitive defect in DS; (2) the information will provide guidance to those developing intervention strategies either early in life or later, when the risk of Alzheimer's disease is significant; and (3) the information will shed light on critical differences between low- and high-functioning individuals with DS, thereby suggesting strategies for helping those individuals with the least positive prognosis.