Project 2-Mapping Cortical Circuit Maturation in High Risk Adolescents

项目 2 - 绘制高危青少年的皮质回路成熟度图

• 批准号: 7333006
• 负责人: Aysenil Belger
• 金额: $ 34.48万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7333006
• 关键词: Adolescence; Adolescent; Affective; Age; Amygdaloid structure; Anisotropy; Anterior; Attention; Basal Ganglia; Brain; Characteristics; Child; Clinical; Cognition; Cognitive; Development; Diffusion; Electroencephalography; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Genetic; Genetic Risk; Goals; Hippocampus (Brain); Image; Individual; Knowledge; Magnetic Resonance Imaging; Maps; Measures; Medial; Neurocognitive; Neurocognitive Deficit; Pathway interactions; Performance; Population; Process; Property; Protocols documentation; Psychotic Disorders; Puberty; Relative (related person); Research; Research Infrastructure; Risk; Schizophrenia; Severities; Shapes; Staging; Structure; Synapses; Time; aged; cognitive function; critical developmental period; endophenotype; executive function; follow-up; genetic profiling; gray matter; neurocognitive test; novel; programs; relating to nervous system; research study; social; white matter

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.

该项目的目的是绘制皮质回路的成熟和高阶认知功能的成熟 儿童和青少年有精神分裂症的遗传风险。执行功能和社会影响处理 精神分裂症患者和遗传高风险（GHR）的人都存在缺陷 疾病，因此代表了精神分裂症的认知内表型。然而，他们的 年轻的GHR个体的特征，发作的时间和特定的神经发育 伴随它们的机制尚不清楚。青春期是成熟的关键时期 这些功能，以及精神病的发作。拟议的研究将探测功能和结构 遗传高风险个体中围腹大脑成熟的变化，并将调查 GHR儿童和青少年的执行控制和社会影响过程。我们会探究关注 以及在60个GHR和60个健康受试者的额叶层状区域的执行和情感处理 使用9-18岁。我们将使用多模式评估方案，包括（a）神经认知测试（b） 功能磁共振成像（fMRI），（c）电生理记录（ERP）和（d）结构 和扩散成像（SMR |和DTI）。在特定AIM 1中，我们将比较遗传的神经认知特征 健康受试者的高风险（GHR）儿童和青少年在横截面上，并进一步评估组 纵向随访的成熟轨迹差异。特定目标2将表征 使用功能磁性 共振成像和电生理记录。额 - 甲状管区域的结构曲线 在GHR中，包括灰质和白质特性在内的GHR青少年将以特定的方式进行评估 目标。最后，特定的目标4将重点关注额叶和额叶的网络级别集成功能 通过探索功能连接之间的关联，GHR儿童和青少年的边缘电路 措施，白质特性和神经认知措施。通过汇集强大的临床高 - 风险研究计划以及一个建立良好且多样化的研究基础设施，该项目有望 公布有关与遗传风险相关的神经发育变化的关键知识 精神分裂症。提出的实验是新颖的，及时的，非常重要，因为它们专注于独特 人口和探测一个独特的皮质发展阶段，这对于理解 精神分裂症中核心神经认知缺陷的病理生理。