Thalamo-cortical circuitry in PVL

PVL 中的丘脑皮质回路

• 批准号: 10757491
• 负责人: Corinna M Bauer
• 金额: $ 40.63万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10757491
• 关键词: Thalamo; cortical; circuitry; PVL

Project Summary/Abstract Infants born prematurely are predisposed to hypoxic-ischemic (HI) injury such as periventricular leukomalacia (PVL), resulting in developmental disturbances to the thalamus, white matter, and cerebral cortex. As a consequence, survivors of PVL frequently demonstrate visual impairments to varying degrees. Because the thalamus is critical to visual processing, visual dysfunctions may be more severe if the thalamus is affected as a consequence of the HI insult. Yet, the effects of PVL on the developing thalamo-cortical network are unclear. In particular, it is currently not known how aberrant thalamo-cortical connectivity or altered volume of thalamic nuclei contribute to the deficits in visual processing that are commonly observed in individuals with PVL. To this end, the overall goal of the current study is to address the hypothesis that visual perceptual processing deficits may be more severe in individuals with PVL who have decreased volume of visual thalamic nuclei, distinct changes in myelination of thalamo-cortical networks, or atypical thalamo-cortical connectivity. We have developed a cutting-edge multimodal MRI approach consisting of morphometric analysis of individual thalamic nuclei, diffusion kurtosis imaging (DKI), high angular resolution diffusion imaging (HARDI), myelin water fraction maps, and network connectivity analyses that will be used in conjunction with a battery of tests of visual perceptual functions to determine the link between thalamic neuronal loss, thalamo-cortical connectivity, and visual perceptual processing abilities. A total of 36 individuals with PVL will be recruited, along with a cohort of 36 typically-developing controls. A rigorous statistical plan will use multiple levels of analysis to investigate the differences in behavioral and neuroimaging variables between individuals with PVL and controls, as well as the correlation between outcome measures. A series of regression analyses will evaluate the associations of neuroimaging variables with PVL and functional vision. Models will also consider the effects of age and gender on neuroimaging and behavioral outcomes. The unique combination of neuroimaging modalities utilized in this proposed study will provide complementary insight regarding the complex interplay between preterm HI damage in PVL and the resulting changes in thalamic development, and ultimately relate these findings to visual perceptual deficits. This study will contribute to our understanding of the impact of PVL on the establishment and myelination of the thalamo-cortical networks involved with visual perceptual processes, providing evidence-based biomarkers that can be used to evaluate future therapeutic approaches.

项目摘要/摘要 早产儿易发生缺氧缺血性损伤，如脑室周围白质软化症 (PVL)，导致丘脑、白质和大脑皮层发育障碍。作为一名 结果，PVL的幸存者经常表现出不同程度的视力障碍。因为 丘脑是视觉处理的关键，如果丘脑受到AS的影响，视觉功能障碍可能会更加严重 这是HI侮辱的后果。然而，PVL对发育中的丘脑-皮质网络的影响尚不清楚。 特别是，目前尚不清楚丘脑皮质连接的异常或丘脑体积的改变 核团是PVL患者常见的视觉处理缺陷的原因之一。至 为此，当前研究的总体目标是解决视觉知觉加工的假设 视觉丘脑核团体积减少的PVL患者的缺陷可能更严重， 丘脑-皮质网络的髓鞘形成明显改变，或不典型的丘脑-皮质连接。我们有 开发了一种尖端的多模式磁共振成像方法，包括对单个丘脑的形态测量分析 细胞核，扩散峰度成像(DKI)，高角分辨率扩散成像(HARDI)，髓鞘水 分数图和网络连通性分析将与一系列测试一起使用 视觉感知功能，以确定丘脑神经元丢失，丘脑皮质连接， 以及视觉感知处理能力。总共将招募36名PVL患者，以及一名 由36名典型的对照组组成的队列。严格的统计计划将使用多个层次的分析来 研究PVL和PVL患者在行为和神经影像指标上的差异 对照，以及结果衡量标准之间的相关性。一系列回归分析将评估 神经影像变量与PVL和功能视力的关系。模型还将考虑这些影响 年龄和性别对神经成像和行为结果的影响。神经成像的独特组合 这项拟议研究中使用的模式将提供关于复杂相互作用的补充见解 PVL的早产HI损害与由此导致的丘脑发育变化之间的关系，并最终相关 这些发现与视觉知觉缺陷有关。这项研究将有助于我们理解PVL的影响 视知觉参与的丘脑-皮质网络的建立和髓鞘形成 提供基于证据的生物标记物，可用于评估未来的治疗方法。