The Brain Wiring of Frontostriatal Connections in Early Psychosis

精神分裂症被认为与大脑连接障碍有关。我们建议调查结构 早期精神病患者额纹状体连接中的连接障碍(大脑连接错误)。的主要关注点 这一提议是额纹状体连接，它是调制额纹状体回路的初始组成部分 精神分裂症和情感性精神病患者的执行功能和奖赏加工受到干扰。我们 计划确定健康对照组(HC)受试者额叶皮质和纹状体之间的正常大脑连接模式， 使用扩散磁共振(DMRI)声道成像，然后测试与该正常模式的偏差， 在早期精神病患者中。由于大脑连接反映了大脑的发育，早期大脑连接错误的衡量标准 精神病可作为早期精神病患者的发育生物学标记物 从早期干预中受益。 我们将分析从早期精神病患者和匹配的HCS患者获得的数据，作为人类 使用我们的结构和dMRI的病例对照设计中的早期精神病的连接组项目(HCP-EP) 协议。使用这些对象允许我们：(1)减轻药物和慢性病的混淆；(2)使用 包括情感性和非情感性精神病亚型的跨诊断方法识别脑生物标记物 作为特定精神病亚型的基础的异常；以及，(3)使用 HCP工具箱。 这项建议的首要目标是研究肥厚性脑病患者正常的额纹状体脑连接模式。 在早期精神病患者中。我们将分析WM连接，以新的方式使用跟踪照相术来测量布线 额纹状体连通性的模式。我们通过研究提出了两种新的和互补的策略来实现这一点 1)脑连接的几何模式；2)这些连接的投影区重叠。 我们有三个目标。(1)确定HCS的额纹状体脑连接模式；(2)确定额纹状体 早期精神病的大脑连接模式；以及(3)研究大脑行为的相关性。我们假设 (1)与早期精神病相比，HCS将表现出额纹状体脑连接的更整合/会聚的模式 患者；B.情感性精神病受试者将呈现中等程度的整合模式 情感性精神病患者和HCS；以及，(2)早期精神病患者和HCS将表现为额纹状体 认知和情感功能的分离。认知控制受损将与较少的 额纹状体联合纹状体回路的整合/会聚模式与奖赏加工意志受损 与额纹状体边缘纹状体回路的整合程度较低的模式有关。我们还将探索性作为一种 生物变量，如性别特定的大脑发育，因此大脑连接，可能在早期精神病中有所不同。 我们希望通过这个项目来证明额纹状体连接在早期精神病中的重要性， 以及我们错误连接的新方法在早期精神病中作为神经成像生物标记物的有用性。

Schizophrenia is thought to be associated with brain dysconnectivity. We propose to investigate structural connectivity disturbances (brain miswiring) in frontostriatal connections in early psychosis. The primary focus of this proposal is frontostriatal connectivity, which is the initial component of frontostriatal circuits that modulate executive function and reward processing, which are disturbed in schizophrenia and affective psychosis. We plan to define the normal brain wiring pattern between frontal cortex and striatum in healthy control (HC) subjects, using diffusion magnetic resonance (dMRI) tractography and, then, to test for deviations from this normal pattern, in early psychosis patients. As brain wiring reflects brain development, measures of brain miswiring in early psychosis could serve as developmental biological markers identifying those early psychosis patients who might benefit from early intervention. We will analyze data obtained from patients with early psychosis and matched HCs as part of the Human Connectome Project for Early Psychosis (HCP-EP) in a case control design using our structural and dMRI protocols. Using these subjects allows us to: (1) mitigate the confounds of medication and chronicity; (2) use a transdiagnostic approach including affective and non-affective psychoses subtypes to identify brain biomarker abnormalities which underlie specific psychosis subtypes; and, (3) perform brain-behavior correlations using the HCP Toolbox. The overarching goal of this proposal is to investigate the normal frontostriatal brain wiring pattern in HCs and in early psychosis. We will analyze WM connections, using tractography in novel ways to measure wiring patterns in frontostriatal connectivity. We propose 2 novel and complementary strategies to do this by studying 1) the geometric pattern of brain connections; and, 2) the overlap of projection zones of these connections. We have 3 aims. (1) to define the frontostriatal brain wiring pattern in HCs; (2) to define the frontostriatal brain wiring pattern in early psychosis; and (3) to investigate brain-behavior correlations. We hypothesize that (1) a. HCs will show a more integrative/convergent pattern of frontostriatal brain wiring than will early psychosis patients; b. affective psychosis subjects will show an intermediate degree of integrative pattern between non- affective psychosis subjects and HCs; and, (2) early psychosis patients and HCs will show frontostriatal dissociations in cognitive and affective function. Impaired cognitive control will be linked to a less integrative/convergent pattern of frontostriatal associative striatum circuitry and impaired reward processing will be linked to a less integrative pattern of frontostriatal limbic striatum circuitry. We will also explore sex as a biological variable as gender-specific brain development, thus brain wiring, may differ in early psychosis. We expect through this project to demonstrate the importance of frontostriatal connectivity in early psychosis, and the usefulness of our novel measures of miswiring as neuroimaging biomarkers in early psychosis.