Thalamic connectivity in recent onset schizophrenia measured by 7T fMRI

 描述(由申请人提供)：精神分裂症(SCZ)是一种主要的公共卫生问题，影响着大约1%的美国人口，并造成毁灭性的后果。丘脑的结构和功能缺陷一直被认为与SCZ有关，丘脑是多个皮质和皮质下回路的临界点。丘脑由多个核组成，每个核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联系进行了重新定义。这些区域太小，常规(3T)fMRI无法分辨，但超高场(7T)fMRI可以分辨。因此，在目标1中，我们建议在7T时使用静息BOLD信号来测试这一假设，即与匹配的健康对照组(每组25人)相比，最近的onst SCZ患者丘脑皮质回路的功能连接受到干扰。根据我们在慢性精神分裂症患者中的初步数据，我们假设在最近发病的SCZ中，特定的丘脑区域将显示出增强的功能连接。我们预测，异常连接将在解剖上与前额叶皮质相连的丘脑亚区最为明显，与其他皮质区域的连接平行但不那么牢固。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通过动脉自旋标记(ASL)和小动脉脑血容量(CBVa)来确定局部全脑和血流量(CBF)，并使用我们团队开发的一种称为流入血管空间占用(IVASO)MRI的新方法来确定小动脉脑血流量(CBVa)。这些措施将使我们能够更好地解读大胆的信号，也可能揭示精神分裂症患者血液流动或血量的异常。我们预测，BOLD检测到的功能连接的有力证据仍将具有独立意义，但边缘发现可能会被血流和容量变化所解释。其次，我们将测试CBF和CBVa在SCZ的内在异常的假设，包括整个大脑，特别是丘脑。如果成功，我们的结果将支持对SCZ和其他精神障碍中这些参数的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.