STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN SCHIZOPHRENIA IN NEUROPSYCHIATRIC DISOR

神经精神疾病中精神分裂症的结构和功能连接

• 批准号: 7669320
• 负责人: Heather Cody Hazlett
• 金额: $ 17.51万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7669320
• 关键词: Affect; Amygdaloid structure; Anatomy; Anisotropy; Anterior; Area; Attention; Automobile Driving; Back; Basal Ganglia; Biological; Biological Neural Networks; Blood; Brain; Brain region; Broca' s area; Cell Nucleus; Chronic; Chronic Schizophrenia; Clinical; Communication; Complex; Computer software; Corpus Callosum; Corpus callosum splenium; Data; Delusions; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Ear; Emotions; Episodic memory; Etiology; Event; Failure; Fiber; Functional Magnetic Resonance Imaging; Functional disorder; Grant; Hallucinations; Hippocampus (Brain); Imaging Techniques; Inferior; Internal Capsule; Language; Left; Lesion; Limb structure; Limbic System; Literature; Location; Magnetic Resonance Imaging; Measurement; Measures; Medial; Memory; Methods; Modeling; Monitor; Myelin; Neurocognitive; Neurologic; Numbers; Operative Surgical Procedures; Paranoia; Parietal; Parietal Lobe; Pathway interactions; Patients; Pattern; Play; Positron-Emission Tomography; Process; Reporting; Research Personnel; Resources; Rest; Retrieval; Right-On; Role; Sampling; Schizophrenia; Seizures; Semantic memory; Semantics; Shapes; Short-Term Memory; Site; Structure; Symptoms; System; Techniques; Technology; Temporal Lobe; Testing; Thalamic Nuclei; Thalamic structure; Thinking; Time; Travel; Visual attention; Work; abstracting; angular gyrus; base; cingulate cortex; cognitive function; design; diffusion anisotropy; executive function; experience; genetic analysis; gray matter; interest; lexical; memory process; memory recognition; memory retrieval; myelination; novel; phonology; rapid growth; research study; semantic processing; size; 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灰质异常方面已经取得了相当大的进展， 在精神分裂症中，在评估白色物质异常或灰质区域之间的白色物质纤维束连接，特别是连接额叶和颞叶的那些方面，进展相对较小。这些纤维束长期以来被认为是精神分裂症的异常。许多后来的研究者假设精神分裂症的某种类型的连接缺陷或断开模型。我们计划在本提案中明确调查此类异常情况。 这项为期三年的提案的首要目标是调查连接异常， 精神分裂症的解剖和功能水平。因此，我们计划采用一种新的， 研究精神分裂症异常脑连接的综合方法，包括 分析白色物质纤维束异常，以及这些通路互连的网络节点。作为一个驱动生物学项目（DBP），这一综合目标将需要高度先进的计算策略和强大的软件实现提供的其他子项目在此赠款。这个项目将强调磁共振扩散张量成像（DTI），一个相对较新的磁共振成像技术，提供了一个独特的机会，调查和量化白色物质异常的大脑。它还将包括功能性磁共振成像（fMRI）探针的工作，情节和语义记忆系统已知是异常的精神分裂症。我们使用功能磁共振成像将特别关注与精神分裂症的病理生理学有关的区域之间的连接，使用记忆激活任务来显示假设的异常。事件相关的言语情景编码和识别记忆任务将针对前额叶和内侧颞叶部位。这项任务是根据我们以前在正常人和接受手术治疗的已知癫痫灶患者中的fMRI经验开发的。早期使用电生理学方法的证据表明，类似的实验对额叶与颞叶病变位置的敏感性，许多PET和fMRI研究表明这些区域与精神分裂症有关。我们将使用n-back范式研究工作记忆系统，该范式已被我们的研究小组证明能强烈激活神经系统患者和对照组的前额叶和顶叶皮层。在PET和fMRI文献中广泛报道了健康对照的类似结果。在本研究中，这项任务将为我们提供一个机会，检查额顶叶连接和基底神经节的利益，也经常被激活的网站。 最后，一个事件相关的语义记忆任务模式后，我们早期的封锁设计 实验将用于激活左下前额和左上级感兴趣的颞区（ROI）。更广泛的PET和fMRI文献通常涉及这些网站的语言和语义记忆检索。这些前沿技术将与相关灰质结构的体积和形状分析以及临床和神经认知评估相结合，以充分表征样本。此外，虽然不是本项目的重点，但我们也将采集所有受试者的血液进行基因分析。