Project 2-Mapping Cortical Circuit Maturation in High Risk Adolescents

这个项目的目标是绘制大脑皮质回路和高阶认知功能的成熟图谱 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 精神分裂症患者和遗传高危(GHR)患者都存在基因缺陷 疾病，因此，它们代表了精神分裂症的认知内表型。然而，他们的 年轻GHR个体的特征、发病时间和特定的神经发育 伴随它们的机制尚不清楚。青春期是儿童发育成熟的关键时期。 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 遗传高危个体青春期周围脑成熟的变化，并将进行调查 GHR儿童和青少年的执行控制和社会情感过程。我们将调查关注度 60名GHR和60名健康受试者额纹-边缘区域的执行和情绪加工 年龄在9-18岁之间。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 弥散成像(SMR|和DTI)。在具体目标1中，我们将比较遗传基因的神经认知特征 对高危(GHR)儿童和青少年进行横断面调查，并进一步评估人群 他们的成熟轨迹与纵向随访的差异。《特定目标2》将描述 应用功能磁学研究GHR儿童青少年额纹边区的功能 磁共振成像和电生理记录。额纹缘区的结构轮廓 在GHR中，青少年，包括灰质和白质属性，将被具体评估 目标。最后，特定的目标4将侧重于额纹和额叶的网络级综合功能- 通过探索功能连接性与GHR儿童和青少年边缘环路的关系 测量、白质特性和神经认知测量。通过将强大的临床兴奋聚集在一起- 风险研究计划和完善和多样化的研究基础设施，该项目承诺 揭示与遗传风险相关的神经发育变化的关键知识 精神分裂症。拟议的实验是新颖的、及时的和非常有意义的，因为它们关注的是一种独特的 并探索大脑皮层发育的一个独特阶段，这对理解 精神分裂症核心神经认知缺陷的病理生理学研究。

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.