Project 2-Mapping Cortical Circuit Maturation in High Risk Adolescents

这个项目的目标是绘制大脑皮层回路和高阶认知功能的成熟图， 有精神分裂症遗传风险的儿童和青少年。执行功能与社会情感加工 缺陷存在于精神分裂症患者和遗传高危（GHR）人群中。 疾病，因此它们代表精神分裂症的认知内表型。但是他们的 年轻GHR个体的特征，其发作的时间，以及特定的神经发育 伴随它们的机制尚不清楚。青春期是一个关键时期， 这些功能，以及精神病的发病。拟议的研究将探讨功能和结构 在遗传高危个体中伴随青春期大脑成熟的变化，并将研究 GHR儿童和青少年的执行控制和社会情感过程。我们会注意到 60名GHR和60名健康人的额纹边缘区执行和情感加工 9-18岁使用。我们将使用多模式评估方案，包括（a）神经认知测试（B） 功能性磁共振成像（fMRI），（c）电生理记录（ERP），和（d）结构 和弥散成像（sMR| DTI）。在具体目标1中，我们将比较遗传性痴呆的神经认知特征。 高危（GHR）儿童和青少年与健康受试者进行横断面比较，并进一步评估组 纵向随访的成熟轨迹的差异。具体目标2将描述 GHR儿童和青少年的额-纹-边缘区功能分布，使用功能磁共振成像技术 共振成像和电生理记录。额-纹-边缘区的结构轮廓 在GHR青少年中，包括灰质和白色物质特性，将在特定的 目标。最后，具体的AIM 4将集中在网络水平的整合功能的额纹和额， GHR儿童和青少年的边缘系统电路，通过探索功能连接之间的关联 测量、白色物质特性和神经认知测量。通过将强大的临床高- 风险研究计划和完善的和多样化的研究基础设施，该项目承诺， 揭示了与遗传风险相关的神经发育变化的关键知识， 精神分裂症这些实验是新颖的，及时的，具有重要意义的，因为它们集中在一个独特的 人口和探测皮层发育的一个独特阶段，这对于理解大脑皮层的发育是至关重要的。 精神分裂症核心神经认知缺陷的病理生理学

The goal of this project is to map the maturation of cortical circuits and higher-order cognitive functions in children and adolescents at genetic risk for schizophrenia. Executive function and social-affective processing deficits are present in both individuals with schizophrenia and in those at genetic-high-risk (GHR) for the illness, and as such they represent cognitive endophenotypes of schizophrenia. Nevertheless, their characteristics in younger GHR individuals, the timing of their onset, and the specific neurodevelopmental mechanisms that accompany them are not known. Puberty is a critical period both for the maturation of these functions, and for the onset of psychosis. The proposed study will probe functional and structural change that accompany peripubertal brain maturation in genetic high risk individuals, and will investigate executive control and social-affective processes in GHR children and adolescents. We' will probe attention and executive and affective processing in fronto-striate-limbic regions in 60 GHR and 60 healthy subjects aged 9-18 using. We will use a multimodal assessment protocol, including (a) neurocognitive testing (b) functional magnetic resonance imaging (fMRI), (c) electrophysiological recordings (ERPs), and (d) structural and diffusion imaging (sMR| and DTI). In Specifc Aim 1, we will compare the neurocognitive profile of genetic high risk (GHR) children and adolescents to healthy subjects cross-sectionally, and further assess group differences in their maturational trajectory with longitudinal follow-ups. Specific Aim 2 will characterize the functional profile of fronto-striate-limbic regions in GHR children and adolescents, using functional magnetic resonance imaging and electrophysiological recordings. The structural profile of fronto-striate-limbic regions in GHR adolescents, including both gray matter and white matter properties, will be assessed in Specific AIMS. Finally, Specific AIM 4 will focus on network level integrative functioning of fronto-striate and fronto- limbic circuitry in GHR children and adolescents by exploring associations between functional connectivity measures, white matter properties and neurocognitive measures. By bringing together a strong clinical high- risk research program and a well established and diverse research infrastructure, this project promises to unveil critical knowledge about the neurodevelopmental changes associated with genetic risk for schizophrenia. The proposed experiments are novel, timely and highly significant for they focus on a unique population and probe a unique stage of cortical development that is critical for understanding the pathophysiology of core neurocognitive deficits in schizophrenia.