Williams Syndrome: Bridging Cognition, Brain and Genes

描述(申请人提供)：这项研究是计划项目：威廉姆斯综合征的一个组成部分和协同部分：桥接认知、大脑和基因，将高级认知功能与其潜在的神经生物学基础和遗传基础联系起来。这个子项目的目标是表征威廉姆斯综合征(WS)患者感觉和认知加工的电生理表型，并将这些表型表达的可变性与大脑结构和功能(项目III)、神经认知(项目V)和遗传特征(项目I)的可变性联系起来。为此，将使用高密度ERP系统记录事件相关电位(ERPs)，以检查与1)背侧和腹侧视觉流的不同激活有关的大脑活动的时间和地形图，2)情绪对面部表情处理和言语陈述性记忆系统的影响，3)遗传变异性和大脑功能的研究：非典型缺失和起源的父母。使用跨项目的类似范例，行为、功能磁共振成像和事件相关电位数据将被用来开发感觉、认知和社会情绪过程的WS表型的跨学科表征。脑功能异常与遗传特征之间的联系(项目I)将通过描述完全缺失的WMS患者的典型活动模式，并将这些模式与具有不同基因特征的个体的ERP进行比较，例如非典型缺失或WS缺失的起源父母。这个项目的头两年已经揭示了一些令人惊讶的发现，包括大脑对视觉刺激的异常活动模式，在大脑皮层/背侧通路和细小/腹侧通路。这些数据与功能磁共振成像数据相结合，可能有助于阐明语言和面部处理等高级认知功能所观察到的非典型脑组织模式的潜在机制。与Project I合作的其他初步发现表明，非典型语言和面孔加工可能与父母起源有关，并与特定基因的表达相互作用。与公共健康的关系：这项研究为我们进一步了解患有特定疾病WS的个人的神经认知发展提供了希望，与其他项目的神经生理学、神经成像、遗传学、细胞和分子研究一起，将帮助我们在更大的人类群体中弥合对认知和基因的理解。

DESCRIPTION (provided by applicant): This research is an integral and synergistic part of the Program Project: Williams Syndrome: Bridging Cognition, Brain and Genes to link higher cognitive functions with their underlying neurobiological basis and genetic foundations. The goal of this subproject is to characterize the electrophysiological phenotypes of sensory and cognitive processing in individuals with Williams Syndrome (WS) and to link variability in the expression of these phenotypes to variability in brain structure and function (Project III), neurocognitive (Project V), and genetic profiles (Project I). To this end, event-related potentials (ERPs) will be recorded using a high-density ERP system to examine the timing and topography of brain activity linked to 1) differential activation of the dorsal and ventral visual streams, 2) the effects of emotion on processing facial expressions and verbal declarative memory systems, 3) Studies of genetic variability and brain function: atypical deletions and parent of origin. Using similar paradigms across projects behavioral, fMRI and ERP data will be used to develop a cross-disciplinary characterization of the WS phenotype for sensory, cognitive and social emotional processes. Links between abnormal brain function and genetic profiles (Project I) will be conducted by characterizing patterns of activity typical of individuals with WMS with a full deletion and comparing these patterns with ERPs from individuals with different genetic profiles such as atypical deletions or parent of origin of the deletion for WS. The first two years of this project have revealed a number of surprising findings including abnormal patterns of brain activity to visual stimuli in both the magno/dorsal and parvo/ventral pathways. These data in collaboration with fMRI data may help elucidate the underlying mechanisms for atypical patterns of brain organization observed for higher cognitive functions such as langauge and face processing. Other prelimiary findings in collaboration with Project I suggest that atypical language and face processing may be related to parent of origin and interactions with the expression of specific genes. Relation to public health: this research offers promise in furthering our understanding of neurocognitive development in individuals with a specific medical condition, WS, that together with neurophysiological, neuroimaging, genetic, cellular, and molecular studies from other projects, will help us bridge an understanding of cognition and gene within the greater human population.