Thalamic connectivity in recent onset schizophrenia measured by 7T fMRI

通过 7T fMRI 测量新近发病的精神分裂症的丘脑连接

• 批准号: 9189741
• 负责人: Jun Hua
• 金额: $ 20.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-07 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9189741
• 关键词: Address; Affect; American; Anatomy; Biological Markers; Biological Process; Biology; Blood Vessels; Blood Volume; Blood flow; Brain; Brain region; Cell Nucleus; Cerebrovascular Circulation; Chronic Schizophrenia; Classification; Cognitive deficits; Data; Diagnosis; Disease; Economics; Effectiveness; Employee Strikes; Functional Magnetic Resonance Imaging; Human; Hypoxia; Individual; Investigation; Investigational Therapies; Lead; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medicine; Mental disorders; Methodology; Methods; Modality; Monitor; Morphology; National Institute of Mental Health; Network-based; Nuclear; Pattern; Phase; Population; Prefrontal Cortex; Public Health; Research Priority; Rest; Risk; Schizophrenia; Sensory; Severities; Signal Transduction; Site; Specificity; Spin Labels; Stimulus; Structure; Symptoms; Technology; Testing; Thalamic Nuclei; Thalamic structure; Work; base; cerebral blood volume; cognitive load; experimental study; in vivo; neuroimaging; neurovascular; novel; outcome forecast; public health relevance; response; social

 DESCRIPTION (provided by applicant): Schizophrenia (scz) is a major public health problem affecting ~1% of the American population with devastating consequences. Structural and functional deficits in the thalamus, a critical point of convergence for multiple cortical and subcortical circuits, have been consistently implicated in scz. The thalamus is composed of multiple nuclei, each with a different pattern of anatomical and functional connectivity. These nuclei have now been redefined based on anatomical connections to other brain regions. These regions are too small to be resolved by conventional (3T) fMRI, but can be resolved by ultra-high field (7T) fMRI. We therefore propose, In aim 1, to use resting BOLD signal at 7T to test the hypothesis that functional connectivity of thalamocortical circuitry in individuals with recent onst scz is disrupted compared to matched healthy controls (N =25 per group). Based on our preliminary data in individuals with chronic schizophrenia, we hypothesize that specific thalamic regions will show enhanced functional connectivity in recent onset scz. We predict that abnormal connectivity will be most evident in the thalamic subregions anatomically connected to prefrontal cortex, with parallel but less robust connectivity to other cortical regions. Secondaril, we predict that symptom severity and cognitive deficits will be correlated with the extent of abnormal connectivity. BOLD signal, however, is strongly modulated by neurovascular function. Therefore, in Aim 2 we will use 7T fMRI to determine regional whole brain and blood flow (CBF) using arterial spin labelling (ASL), and arteriolar cerebral blood volume (CBVa) using a new method developed by our group called inflow vascular space occupancy (iVASO) MRI. These measures will enable us to better interpret BOLD signals, and may also reveal abnormalities in blood flow or blood volume in schizophrenia. We predict that robust evidence of functional connectivity detected by BOLD will remain independently significant, but that marginal findings may be accounted for by blood flow and volume changes. Secondarily, we will test the hypotheses that CBF and CBVa are intrinsically abnormal in scz, both across the brain and specifically in the thalamus. If successful, our results will support larger, longitudinal studies f these parameters in scz and other psychiatric disorders.

 描述（由适用提供）：精神分裂症（SCZ）是影响约1％的美国人口的主要公共卫生问题，并带来毁灭性后果。丘脑中的结构和功能缺陷，这是多层皮质和皮质下回路的临界点，一直与SCZ有关。丘脑由多个核心组成，每个核会都有不同的解剖和功能连接模式。这些核现已根据与其他大脑区域的解剖联系重新定义。这些区域太小，无法通过常规（3T）fMRI解决，但可以通过超高场（7T）fMRI解决。因此，我们建议在AIM 1中使用7T处的静息BOLD信号来检验以下假设：与匹配的健康对照组相比，近期ONST SCZ个体的丘脑皮质电路的功能连通性受到干扰（每组n = 25）。基于我们在慢性精神分裂症患者中的初步数据，我们假设特定的丘脑区域将在最近的SCZ中显示出增强的功能连接性。我们预测，异常连通性将是与前额叶皮层相关的丘脑子区域中的大多数证据，与其他皮质区域的连通性具有平行但较差的连通性。次要，我们预测症状严重程度和认知定义将与异常连通性的程度相关。然而，大胆的信号受神经血管功能的强烈调节。因此，在AIM 2中，我们将使用动脉自旋标记（ASL）（ASL）和动脉脑血容量（CBVA）使用7T fMRI来确定区域全脑和血流（CBF），并使用我们的小组使用称为流入血管空间占用（IVASO）MRI开发的新方法。这些措施将使我们能够更好地解释大胆的信号，并且还可能揭示精神分裂症中血流或血量的异常。我们预测，BOLD检测到的功能连接性的强大证据将保持独立意义，但是边际发现可能是由血流和体积变化来解释的。其次，我们将测试CBF和CBVA在SCZ中本质上异常的假设，无论是在整个大脑中，特别是在丘脑中。成功，我们的结果将支持SCZ和其他精神疾病中这些参数的更大的纵向研究。