Thalamo-cortical circuitry in PVL

PVL 中的丘脑皮质回路

• 批准号: 10681328
• 负责人: Corinna M Bauer
• 金额: $ 42.58万
• 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/10681328
• 关键词: 3-Dimensional; Address; Affect; Anisotropy; Anterior; Atlases; Atrophic; Behavior; Behavioral; Bilateral; Biological Markers; Brain; Brain Hypoxia-Ischemia; 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; 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; Predisposition; Premature Infant; Process; Pulvinar structure; Regression Analysis; Resolution; Rest; Retrograde Degeneration; Series; Severities; Survivors; Testing; Thalamic Nuclei; Thalamic structure; Therapeutic; Vision; Visual; Visual impairment; Water; age effect; behavioral outcome; cohort; evidence base; gray matter; hypoxic ischemic injury; insight; morphometry; multimodal neuroimaging; 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.

项目总结/摘要 早产儿易发生缺氧缺血性损伤，如脑室周围白质软化 (PVL)导致丘脑、白色物质和大脑皮层发育障碍。作为 因此，PVL的幸存者经常表现出不同程度的视力障碍。因为 丘脑对视觉处理至关重要，如果丘脑受到影响， 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，目前尚不清楚异常的丘脑-皮质连接或丘脑体积的改变是如何发生的。 核导致视觉处理的缺陷，这在PVL患者中是常见的。到 为此，本研究的总体目标是解决视觉知觉加工的假设， 在视觉丘脑核体积减少的PVL患者中，缺陷可能更严重， 丘脑-皮质网络髓鞘形成的明显变化，或非典型的丘脑-皮质连接。我们有 开发了一种尖端的多模式MRI方法，包括对单个丘脑的形态学分析， 核，弥散峰度成像（DKI），高角分辨率弥散成像（HARDI），髓鞘水 分数图和网络连通性分析，这些分析将与一系列测试结合使用， 视觉感知功能，以确定丘脑神经元损失，丘脑-皮质连接， 和视觉感知处理能力。总共将招募36名PVL患者，并沿着 36例典型发育对照组。一个严格的统计计划将使用多层次的分析， 研究PVL患者和 控制，以及结果测量之间的相关性。一系列回归分析将评估 神经影像学变量与PVL和功能性视觉的相关性。模型还将考虑 年龄和性别对神经影像学和行为结果的影响。神经影像学的独特组合 在这项拟议的研究中使用的模式将提供关于复杂的相互作用的补充见解 PVL中早产HI损伤与丘脑发育的变化之间的关系，并最终与 这些发现与视觉感知缺陷有关。本研究将有助于我们了解PVL的影响 丘脑-皮层视知觉网络的建立和髓鞘形成 过程，提供基于证据的生物标志物，可用于评估未来的治疗方法。