Quantitative Neuroimaging in Psychosis; DTI Studies

描述（由申请人提供）：来自多个来源的证据表明精神分裂症患者的分布式皮质网络功能障碍，其定义为由定义的认知任务引起的异常激活和激活网络中不同节点之间活动的相关异常相关性。这些异常的过度激活或激活不足被假设为根据任务类型和难度水平以及当前症状特征而变化。目前的提案是对PI现有MERIT奖项的补充，该奖项建议增加弥散张量成像（DTI），以进一步提高我们记录精神分裂症功能障碍回路异常的能力。资助父母补助金的总体目标是建立在以前从Pi实验室收集的数据基础上，这些数据涉及异模态关联新皮质网络（HASC）功能障碍在精神分裂症的病理生理学中发挥核心作用，以更好地定义和理解这种功能障碍。该提案结合了临床评估，功能磁共振成像任务开发和数据分析，认知评估和详细的定量脑结构测量方面的专业知识，并建议增加DTI。目前资助的工作利用功能磁共振成像（fMRI）解剖HASC功能障碍，使用一个全面的电池的良好表征的认知激活范例，其中任务的表现可以表征内部和外部的扫描仪。它检查了100名在功能、功能和认知方面得到良好评估的SZ患者，这些患者接受稳定剂量的第二代抗精神病药物治疗，并与100名匹配的、特征异常良好的健康对照受试者进行了比较。后者正在参与一项正在进行的代表性人口研究，通常老化，从相同的集水区作为我们的病人。除了评估使用激活HASC网络中不同节点的3个认知探测任务收集的fMRI激活模式外，我们还使用MRI形态测量法测量相同脑区的体积，以探索相关的结构/功能关系。我们还将研究功能磁共振成像任务不相关的同步模式，以解决可能的组间性能差异。我们现在建议将DTI评估添加到examine 1连接性。这些数据将被输入结构方程模型，以允许在SZ的HASC脑功能障碍的多个方面进行彻底检查，并探讨大脑结构，功能和连接异常如何与假定的潜在的神经和认知定义的亚型。此外，新的数据融合技术将被用于联合收割机信息跨成像模式。

DESCRIPTION (provided by applicant): Evidence from multiple sources implicates dysfunction in distributed cortical networks in individuals with schizophrenia, defined both by aberrant activation provoked by defined cognitive tasks and by associated abnormal correlation of activity between different nodes in the activated network. These abnormal over- or under-activations are hypothesized to vary in response to task type and difficulty level, and to current symptom profile. The current proposal is a supplement to an existing MERIT award to the PI, that proposes to add Diffusion Tensor Imaging (DTI) to further enhance our ability to document abnormalities in a circuit that is dysfunctional in schizophrenia. The overall aim of the funded parent grant is to build on previously gathered data from the Pi's Lab that implicated dysfunction of the heteromodal association neocortical network (HASC) as playing a central role in the pathophysiology of schizophrenia, to better define and understand this dysfunction. This proposal combines expertise in clinical assessment, fMRI task development and data analysis, cognitive assessment and detailed quantitative structural brain measurement, with the proposed addition of DTI. The currently funded work utilizes functional MRI (fMRI) to dissect HASC dysfunction using a comprehensive battery of well-characterized cognitive activation paradigms, where task performance can be characterized both inside and outside the scanner. It examines a diverse population of 100 symptomatically, functionally and cognitively well-assessed patients with SZ on stable doses of second-generation antipsychotic medications, compared to 100 matched, exceptionally well characterized healthy control subjects. These latter are participating in an ongoing representative population study of usual aging, drawn from the same catchment areas as our patients. In addition to assessing fMRI activation patterns gathered using 3 cognitive probe tasks that activate different nodes in the HASC network, we are measuring volumes of the same brain regions using MRI morphometry, to explore structure/function relationships correlative^. We will also examine fMRI task-uncorrelated synchrony patterns to address possible between-group performance differences. We now propose to add DTI assessments to examine1 connectivity. These data will be entered into structural equation models to permit a thorough examination of multiple aspects of HASC brain dysfunction in SZ and explore how brain structure, function and connectivity abnormalities relate to putative underlying symptomatically- and cognitively-defined subtypes. In addition, novel data fusion techniques will be used to combine information across imaging modalities.