Neurovascular and Neuroplastic Contributions to Visual Recovery After Stroke

神经血管和神经可塑性对中风后视力恢复的贡献

• 批准号: 10231070
• 负责人: Colleen L Schneider
• 金额: $ 4.18万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2022-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231070
• 关键词: Adult; Affect; Animals; Basic Science; Biological; Blindness; Blood; Blood Vessels; Blood flow; Brain; Cerebrovascular Circulation; Cerebrum; Cessation of life; Clinical; Clinical Trials; Cognitive; Contracts; Contralateral; Coupling; Data; Deafferentation procedure; Edema; Experimental Designs; Functional Magnetic Resonance Imaging; Goals; Grant; Human; Impairment; Individual; Ischemia; Lead; Lesion; Location; Longitudinal Studies; Measures; Mediator of activation protein; Methodology; Methods; Modeling; Motor; Motor Cortex; Neurologic; Neuronal Injury; Neuronal Plasticity; Neurons; Ophthalmology; Outcome; Oxygen; Oxygen Consumption; Patients; Perimetry; Phase; Physicians; Recovery; Rehabilitation therapy; Research; Research Project Grants; Running; Scientist; Secondary to; Sensory; Specificity; Statistical Data Interpretation; Stimulus; Stroke; Structure of posterior cerebral artery; Synapses; Testing; Time; Tissues; Training; Treatment outcome; United States; Vision; Visual; Visual Cortex; Visual Fields; Visual Perception; Visual system structure; blind; blood oxygen level dependent; career; clinical outcome measures; clinical practice; clinically significant; computer program; cytotoxic; deprivation; disability; experience; hemodynamics; hypoperfusion; improved; interest; ischemic injury; neuroimaging; neurovascular; neurovascular coupling; patient population; post stroke; preference; prognostic; programs; receptive field; rehabilitation strategy; relating to nervous system; repaired; research clinical testing; response; restoration; retinotopic; stroke patient; stroke recovery; synaptogenesis; visual stimulus

Abstract Stroke is a leading cause of serious long-term adult-onset disability in the United States, with 25% of stroke patients experiencing some type of visual field deficit. Stroke in the territory of the posterior cerebral artery (PCA) causes blindness in all or parts of the visual hemi-field contralateral to the lesion. This blind field begins to contract within the first 10 days following stroke with some patients continuing to improve out to 6 months. While about 50% of patients experience some degree of visual improvement, only 12.5% of patients experience complete recovery. The underlying mediators of recovery remain poorly understood due to the brain's multifaceted response to ischemic injury. We test the hypothesis that post-stroke recovery is associated with: 1) neurovascular repair and 2) experience-dependent induction of neuroplasticity. To test this hypothesis, the proposed project details a longitudinal study of changes in visual perception and neural activity in stroke patients at 1 week, 1 month, and 3 months after stroke in the territory of the PCA. Visual recovery will be quantified with a clinical neuro-ophthalmological test of perceptual vision and correlated with different measures of neural activity using functional magnetic resonance imaging (fMRI). Aim 1 tests the hypothesis that spontaneous visual recovery at 1 month, but not additional spontaneous recovery at 3 months, is specifically due to normalization of the perilesional tissue's neurovascular response to visual stimuli. This normalization could reflect recovery of previously dysfunctional ischemia-resilient neurons and/or vascular repair. The neurovascular response will be quantified at each time point with fMRI by calculating the time to peak activation following presentation of a full-field visual stimulus. Aim 2 tests the hypothesis that tuning curve widening in perilesional cortex differentially underlies spontaneous perceptual visual recovery at 1 month, while shifts in the preferred retinotopic focus of perilesional voxels differentially explains additional spontaneous visual recovery at 3 months. This hypothesis is consistent with a model of post-stroke neuroplasticity in the motor cortex in which there is an initial non-specific expansion of activation that later consolidates and regains specificity but for a different location. These changes in a perilesional voxel's activation profile will be quantified from fMRI runs in which the patient views a pseudo-random presentation of flickering checkerboard wedges in 12 non-overlapping locations. The degree to which each voxel responds to each wedge location will constitute that voxel's spatial location tuning curve. Understanding how the brain's response after stroke influences visual perception will inform neuroplasticity research, clinical targets for rehabilitation treatments, outcome measures for clinical trials, and best practices for conducting fMRI research in a patient population with altered neurovascular functioning.

摘要 在美国，中风是严重的长期成人发病残疾的主要原因，25%的中风 出现某种类型的视野缺陷的患者。大脑后动脉范围内的卒中 (PCA)导致病变对侧的全部或部分视觉半视野失明。这片盲区开始了 在中风后的头10天内收缩，一些患者持续改善到6个月。 虽然大约50%的患者经历了不同程度的视力改善，但只有12.5%的患者 体验完全康复。经济复苏的潜在调解人仍然知之甚少，因为 脑对缺血性损伤的多方面反应。我们检验了中风后康复与 与：1)神经血管修复和2)经验依赖的神经可塑性诱导。为了检验这一假设， 该项目详细介绍了对中风患者视觉感知和神经活动变化的纵向研究。 患者分别于卒中后1周、1个月、3个月在PCA辖区内就诊。视觉恢复将是 通过临床神经眼科知觉视力测试进行量化，并与不同的 使用功能磁共振成像(FMRI)测量神经活动。Aim 1检验假设 视力在1个月后自然恢复，但在3个月后不再自然恢复，是 特别是由于病变周围组织对视觉刺激的神经血管反应正常化。这 正常化可以反映先前功能失调的抗缺血神经元和/或血管的恢复 修理。神经血管反应将在每个时间点用fMRI进行量化，方法是计算 呈现全视野视觉刺激后的峰值激活。目标2测试调谐曲线的假设 皮损周围皮质的扩大与1个月时的自发知觉视觉恢复不同 皮损周围体素的首选视网膜定位焦点的移动不同地解释了额外的自发 术后3个月视力恢复。这一假说与中风后神经可塑性的模型一致 运动皮质，在其中有一个最初的非特异性激活扩展，后来巩固和恢复 特异性，但针对不同的位置。周围体素的激活轮廓中的这些变化将被量化 从fMRI运行中，患者在其中查看闪烁的棋盘楔形的伪随机演示 12个不重叠的位置。每个体素对每个楔形位置的响应程度将构成 该体素的空间位置调谐曲线。了解中风后大脑的反应如何影响视觉 知觉将为神经可塑性研究、康复治疗的临床目标、结果测量提供信息 用于临床试验，以及在患者群体中进行功能磁共振研究的最佳实践 神经血管功能。