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存在功能障碍，其定义是由定义的认知任务引起的异常激活，以及激活网络中不同节点之间活动的相关异常。这些异常的过度激活或不足激活被假设为对任务类型、难度水平和当前症状的反应不同。目前的提案是对PI现有的MERIT奖的补充，该奖项提议增加扩散张量成像（DTI），以进一步增强我们记录精神分裂症中功能失调回路异常的能力。资助的父母资助的总体目标是建立在先前从Pi的实验室收集的数据，这些数据暗示异模联合新皮层网络（HASC）的功能障碍在精神分裂症的病理生理学中起着核心作用，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、fMRI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性磁共振成像（fMRI）来剖析HASC功能障碍，使用全面的认知激活范式，其中任务表现可以在扫描仪内部和外部进行表征。该研究检查了100名在症状、功能和认知方面得到良好评估的SZ患者，这些患者使用稳定剂量的第二代抗精神病药物，与100名匹配的、特征特别明确的健康对照受试者进行了比较。这些人正在参与一项正在进行的典型人口老龄化研究，他们与我们的病人来自同一集水区。除了使用激活HASC网络不同节点的3个认知探针任务来评估fMRI激活模式外，我们还使用MRI形态测量法测量相同大脑区域的体积，以探索结构/功能相关关系^。我们还将研究功能磁共振成像任务不相关的同步模式，以解决组间可能的表现差异。我们现在建议增加DTI评估来检查连通性。这些数据将被输入到结构方程模型中，以允许对SZ的HASC脑功能障碍的多个方面进行彻底检查，并探索大脑结构、功能和连接异常与假定的潜在症状和认知定义亚型之间的关系。此外，新的数据融合技术将用于跨成像模式整合信息。

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.