Thalamo-cortical circuitry in PVL

PVL 中的丘脑皮质回路

• 批准号: 10237115
• 负责人: Corinna M Bauer
• 金额: $ 41.11万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 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/10237115
• 关键词: 3-Dimensional; Address; Affect; Anisotropy; Anterior; Atlases; Atrophic; Behavior; Behavioral; Bilateral; Biological Markers; Brain; Brain Injuries; Cell Nucleus; Cerebral cortex; Characteristics; Communication; Complex; Data; Development; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Functional Magnetic Resonance Imaging; Future; Gender; Geniculate body structure; Goals; Habilitation; Histologic; Hypoxia; Image; Impairment; Individual; Infant; Injury; Intervention; Link; Long-Term Effects; Magnetic Resonance Imaging; Maps; Measures; Methodology; Modality; Modeling; Myelin; Oligodendroglia; Outcome; Outcome Measure; Parents; Perinatal Hypoxia; Periventricular Leukomalacia; Persons; Premature Infant; Process; Pulvinar structure; Regression Analysis; Resolution; Rest; Retrograde Degeneration; Series; Severities; Structure; Survivors; Testing; Thalamic Nuclei; Thalamic structure; Therapeutic; Vision; Visual; Visual impairment; Water; age effect; base; behavioral outcome; cohort; evidence base; gray matter; hypoxic ischemic injury; insight; morphometry; multimodality; myelination; neuroimaging; neuron loss; preservation; prognostic; recruit; segregation; tractography; visual dysfunction; visual processing; white matter; white matter injury

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 过早出生的婴儿易于缺氧 - 缺血（HI）损伤，例如脑室脑白血病。 （PVL），导致对丘脑，白质和脑皮质的发育干扰。作为 结果，PVL的幸存者经常在不同程度上表现出视觉障碍。因为 丘脑对于视觉处理至关重要，如果丘脑受到影响，视觉功能障碍可能会更严重 HI侮辱的结果。然而，尚不清楚PVL对发展中丘脑 - 皮质网络的影响。 特别是，目前尚不清楚丘脑 - 皮质连通性异常或丘脑体积变化如何 核有助于在PVL个体中通常观察到的视觉处理缺陷。到 当前研究的总体目标是解决视觉感知处理的假设 PVL的个体的缺陷可能更严重，而视觉丘脑核的体积减少， 丘脑皮质网络的髓鞘形成明显变化，或非典型的丘脑 - 皮层连通性。我们有 开发了一种尖端的多模式MRI方法，该方法包括单个丘脑的形态分析 细胞核，扩散峰度成像（DKI），高角度分辨率扩散成像（HARDI），髓鞘水 分数图和网络连接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丧失，丘脑 - 皮层连接性之间的联系， 和视觉感知处理能力。总共将招募36名患有PVL的人 共有36个通常开发控件的队列。严格的统计计划将使用多个级别的分析来 研究PVL和PVL个体之间的行为和神经影像变量的差异 对照以及结果度量之间的相关性。一系列回归分析将评估 神经成像变量与PVL和功能视觉的关联。模型还将考虑效果 关于神经影像和行为结果的年龄和性别。神经影像的独特组合 这项拟议的研究中使用的方式将提供有关复杂相互作用的互补见解 在PVL中的早产HI损害与丘脑发育的结果变化之间，并最终与 这些发现对视觉感知缺陷。这项研究将有助于我们理解PVL的影响 关于与视觉感知有关的丘脑 - 金属网络的建立和髓鞘 提供基于证据的生物标志物的过程，可用于评估未来的治疗方法。