Thalamic connectivity in recent onset schizophrenia measured by 7T fMRI

 精神分裂症（SCZ）是一种主要的公共卫生问题，影响约1%的美国人口，具有毁灭性的后果。丘脑是多个皮层和皮层下回路的关键汇聚点，其结构和功能缺陷一直与scz有关。丘脑由多个核团组成，每个核团具有不同的解剖和功能连接模式。这些核团现在已经根据与其他大脑区域的解剖学联系重新定义。这些区域太小，无法通过常规（3T）fMRI来分辨，但可以通过超高场（7T）fMRI来分辨。因此，我们建议，在目标1中，使用7T下的静息BOLD信号来检验以下假设：与匹配的健康对照组相比，最近onst scz患者的丘脑皮质回路的功能连接被破坏（每组N =25）。基于我们对慢性精神分裂症患者的初步研究数据，我们假设在新近发病的scz中，特定的丘脑区域会显示出增强的功能连接。我们预测，异常的连接将是最明显的解剖学上连接到前额叶皮层的丘脑分区，与其他皮质区域的平行，但不太强大的连接。其次，我们预测症状的严重程度和认知缺陷将与异常连接的程度相关。然而，BOLD信号受到神经血管功能的强烈调制。因此，在目标2中，我们将使用7T fMRI来确定局部全脑和血流量（CBF）使用动脉自旋标记（ASL），和小动脉脑血容量（CBVa）使用我们的小组开发的一种新方法称为流入血管空间占用（iVASO）MRI。这些措施将使我们能够更好地解释BOLD信号，也可能揭示精神分裂症的血流量或血容量异常。我们预测，BOLD检测到的功能连接的有力证据将保持独立的重要性，但边缘的发现可能是由血流和体积的变化。其次，我们将测试的假设，CBF和CBVa是内在异常的SCZ，无论是在整个大脑，特别是在丘脑。如果成功，我们的结果将支持对scz和其他精神疾病的这些参数进行更大规模的纵向研究。

 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.