STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN SCHIZOPHRENIA

精神分裂症的结构和功能连接

• 批准号: 6988900
• 负责人: ANDREW J SAYKIN
• 金额: $ 27.14万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-17 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6988900
• 关键词: bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain mapping; brain morphology; central neural pathway /tract; cooperative study; functional magnetic resonance imaging; human subject; intercellular connection; magnetic resonance imaging; patient oriented research; positron emission tomography; schizophrenia; synapses; white matter

Although considerable progress has been made in delineating MRI gray matter abnormalities in schizophrenia, relatively little progress has been made in evaluating white matter abnormalities, or the white matter fiber tract connections between gray matter regions, particularly those that connect the frontal and temporal lobes. These tracts that have long been thought to be abnormal in schizophrenia. Many subsequent investigators have hypothesized some type of connectivity deficit or disconnection model of schizophrenia. We plan to explicitly investigate such anomalies in this proposal. The overarching aim of this three-year proposal is to investigate abnormalities of connectivity at an anatomic and functional level in schizophrenia. Accordingly, we plan to employ a novel and integrative approach to investigating abnormal brain connectivity in schizophrenia, including an analysis of white matter fiber tract abnormalities, as well as the network nodes that these pathways interconnect. As a Driving Biological Project (DBP), this integrative aim will require the highly advanced computational strategies and robust software implementation provided by other subprojects in this grant. This project will emphasize MR Diffusion Tensor Imaging (DTI), a relatively new MR imaging technique that affords a unique opportunity to investigate and quantify white matter abnormalities in the brain. It will also include functional MRI (fMRI) probes of working, episodic, and semantic memory systems known to be abnormal in schizophrenia. Our use of fMRI will focus specifically on connectivity among regions implicated in the pathophysiology of schizophrenia using memory activation tasks to bring out the hypothesized abnormalities. An event related verbal episodic encoding and recognition memory task will target prefrontal and medial temporal sites. This task was developed based on our prior fMRI experience in normals and in patients with known seizure foci undergoing surgical treatment. Earlier evidence using electrophysiological methods suggested sensitivity of similar experiments to frontal vs. temporal lobe lesion location and numerous PET and fMRI studies have implicated these regions in schizophrenia. We will investigate the working memory system with fMRI using the n-back paradigm which has been shown by our group to robustly activate the prefrontal and parietal cortex in neurological patients and controls. Similar results in healthy controls have been widely reported in the PET and fMRI literature. In the present study, this task will afford us an opportunity to examine fronto-parietal connectivity and basal ganglia sites of interest that are also often activated. Finally, an event-related semantic memory task patterned after our earlier blocked design experiments will be used to activate left inferior prefrontal and left superior temporal regions of interest (ROIs). The broader PET and fMRI literature typically implicates these sites for language and semantic memory retrieval. These leading edge technologies will be integrated with volumetric and shape analyses of implicated gray matter structures as well as clinical and neurocognitive assessments to fully characterize the sample. In addition, although not the focus of this project, we will also collect blood from all subjects for genetic analysis.

尽管在描述MRI灰质异常方面取得了很大进展 精神分裂症，在评估白质异常方面取得的进展相对较少，或者是灰质区域之间的白质纤维道，尤其是那些连接额叶和颞叶的纤维区域之间的连接。这些长期以来一直认为在精神分裂症中是异常的区域。随后的许多研究人员假设精神分裂症的某种类型的连通性赤字或断开模型。我们计划在该提案中明确调查此类异常。 该三年提案的总体目的是调查连通性异常 精神分裂症的解剖和功能水平。因此，我们计划采用小说， 调查精神分裂症异常大脑连通性的综合方法，包括 对这些途径相互连接的网络节点的白质纤维道异常分析。作为驾驶生物学项目（DBP），这种综合目标将需要该赠款中其他副标题提供的高级计算策略和强大的软件实施。该项目将强调MR扩散张量成像（DTI），这是一种相对较新的MR成像技术，为研究和量化大脑中的白质异常提供了独特的机会。它还将包括工作，情节和语义记忆系统的功能性MRI（fMRI）探针，已知在精神分裂症中是异常的。我们对fMRI的使用将专门集中于使用记忆激活任务与精神分裂症的病理生理学的区域之间的连通性，以提出假设的异常。与事件相关的口头情节编码和识别记忆任务将针对前额叶和内侧时间位点。这项任务是根据我们先前在正常情况和接受手术治疗的已知癫痫发作焦点患者的功能磁共振成像经验而开发的。使用电生理方法的较早证据表明，相似的实验对额叶与颞叶病变位置的敏感性以及许多PET和fMRI研究已暗示了这些地区在精神分裂症中。我们将使用fMRI使用N-BACK范式调查工作记忆系统，该范式已得到我们组的表明，可以在神经系统患者和对照组中稳健地激活前额叶和顶叶皮层。在PET和FMRI文献中，已广泛报道了健康对照的类似结果。在本研究中，这项任务将使我们有机会检查额骨 - 额 - 神经节感兴趣的位点，这些连通性也经常被激活。 最后，与事件相关的语义记忆任务在我们较早的封锁设计之后构成了图案 实验将用于激活左下的前额叶和左上颞叶（ROI）。更广泛的宠物和功能磁共振成像文献通常将这些站点牵涉到语言和语义记忆检索。这些前缘技术将与涉及的灰质结构以及临床和神经认知评估的体积和形状分析集成，以充分表征样本。此外，尽管不是该项目的重点，但我们还将从所有受试者中收集血液进行遗传分析。