The function of descending and ascending pathways in spastic hypertonia and hyperreflexia after stroke

下行和上升通路在脑卒中后痉挛性肌张力增高和反射亢进中的作用

• 批准号: 10633964
• 负责人: Shahabeddin Vahdat
• 金额: $ 39.86万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633964
• 关键词: Affect; Anterolateral; Biomechanics; Brain; Brain imaging; Chronic; Clinical Management; Clinical Trials; Contracture; Contralateral; Data; Dorsal; Early Diagnosis; Electromyography; Electrophysiology (science); Felis catus; Fiber; Flexor; Functional Magnetic Resonance Imaging; Goals; Hand; Hand functions; Handedness; Hemiplegia; Human; Hyperactivity; Hyperreflexia; Impairment; Ipsilateral; Knowledge; Lead; Lesion; Manuals; Measurement; Measures; Medial; Mental Depression; Methods; Modeling; Motor; Motor Neurons; Motor Pathways; Movement; Muscle; Muscle Hypertonia; Muscle Tonus; National Institute of Neurological Disorders and Stroke; Neurobiology; Noise; Outcome Measure; Pain; Pathway interactions; Peripheral; Play; Primates; Prognosis; Prognostic Factor; Protocols documentation; Public Health; Recovery of Function; Reflex action; Research; Resistance; Resolution; Role; Sensory; Signal Transduction; Spinal; Spinal Cord; Stimulus; Stretching; Symptoms; Testing; Theoretical model; Torque; Translating; Upper Extremity; Vertebral column; Work; Wrist; biomarker validation; dorsal column; dorsal horn; effective therapy; follow-up; grasp; heat stimulus; motor impairment; nervous system disorder; neural; neural model; neuroimaging; neuroimaging marker; neuromechanism; post stroke; preclinical study; response; reticulospinal tract; somatosensory; spasticity; spinal pathway; stretch reflex; stroke patient; stroke survivor

This study will target a critical knowledge gap in our understanding of the neural mechanisms underlying upper limb poststroke spasticity, by directly assessing the descending motor and ascending sensory pathways in hand function. Spasticity is one of the major motor impairments after stroke that typically begins to emerge several weeks poststroke, impedes upper limb functional recovery, and gives rise to complications such as weakness, contractures, and pain. It is traditionally characterized by a velocity-dependent increase in muscle tone (hypertonia) and increased spinal stretch reflex (hyperreflexia). Although the peripheral and spinal signatures of spasticity have been extensively studied, its underlying brain mechanisms and brain-spinal pathways are still controversial. This understanding is critically needed for resolving the current limitations in clinical management of spasticity related to its early diagnosis, identification of prognostic factors, and lack of effective treatments targeting the origin of the impairments rather than its symptoms. Preclinical studies have shown that lesions of descending motor pathways including the reticulospinal tract (RST) may lead to spastic hypertonia after stroke. In contrast, changes in the spinal sensory-motor circuits and the ascending sensory projections may underlie hyperreflexia after stroke. Yet it is unclear how brain lesions after stroke lead to these remote changes in the spinal cord circuit. Several theoretical models backed by early electrophysiological work in cats propose that an imbalance of inhibitory and excitatory projections from the dorsal and medial RST plays a critical role in spasticity. However, emerging evidence in primates suggests that the type of RST projections (inhibitory/excitatory) does not follow a dorsal/medial organization, as presumed in current models of spasticity, but depends on the laterality of projections. In this proposal, we aim to translate these new findings to humans, and examine their relevance in poststroke spasticity. Our central hypothesis is that in stroke survivors with spasticity, the imbalanced activation of ipsilateral vs contralateral RST is directly related to spastic hypertonia, while the hyperactivity of dorsal column somatosensory projections is related to spastic hyperreflexia. To test this hypothesis, we will employ a powerful neuroimaging method using simultaneous spinal cord–brain functional magnetic resonance imaging (fMRI) in chronic hemiplegic stroke patients with and without upper limb spasticity, as well as healthy controls. Using this method, we will assess the function of major descending (corticospinal, RST) and ascending (dorsal column, anterolateral tract) pathways during hand motor and sensory functional tasks. We will determine how these neuroimaging markers relate to spastic hypertonia and hyperreflexia, as evaluated by reliable biomechanical and electrophysiological measurements. Overall, the proposed projects will advance our understanding of the neurobiological basis of poststroke spasticity, offer new quantitative neuroimaging markers for accurate prognosis of spastic complications, and provide outcome measures for evaluating what treatments most directly target the neural origins of spasticity.

这项研究将针对我们对上层神经机制的理解的关键知识差距 肢体中风后痉挛，直接评估降降电动机和上升的感觉途径 手功能。痉挛是中风后通常开始出现的主要运动障碍之一 中风后数周，阻碍上肢的功能恢复，并引起并发症，例如 弱点，染色和痛苦。传统上，它的特征是肌肉的速度依赖性增加 张力（高血压）和脊柱拉伸反射（高反射症）。虽然外围和脊柱 痉挛的特征已广泛研究，其潜在的大脑机制和脑脊柱 途径仍然存在争议。解决当前的局限性是至关重要的 与其早期诊断，预后因素识别以及缺乏痉挛的临床管理 针对损害起源而不是其症状的有效治疗方法。临床前研究已有 表明包括网状途径在内的降落电路病变（包括网状区域（RST））可能导致痉挛 中风后的高血压。相反，脊柱感觉运动电路和上升感觉的变化 预测可能是中风后的超反射症。然而，目前尚不清楚中风后的脑病变如何导致这些 脊髓电路的远程变化。几种由早期电生理工作支持的理论模型 在猫的建议中，背侧和媒体首次戏剧的抑制和兴奋性项目的失衡 在痉挛中的关键作用。但是，初级的新兴证据表明REST项目的类型 （抑制性/兴奋性）不遵循当前痉挛模型中提出的背或媒体组织 但取决于项目的横向性。在此提案中，我们旨在将这些新发现转化为人类 并检查它们在中风后痉挛中的相关性。我们的核心假设是，在中风冲浪者中 痉挛性，同侧与对侧RST的不平衡激活与痉挛性高血症直接相关， 虽然背侧柱体感的多动症与痉挛性高反射症有关。测试 这个假设，我们将使用同时使用脊髓 - 脑使用强大的神经影像学方法 慢性偏瘫卒中患者有或没有上部的功能磁共振成像（fMRI） 肢体痉挛以及健康对照。使用此方法，我们将评估主要降序的功能 （皮质脊髓，第一）和手动马达期间的上升（背侧柱，前外侧区）途径 感官功能任务。我们将确定这些神经成像标记与痉挛性高血压和 通过可靠的生物力学和电生理测量值评估，过度反射症。总体而言， 拟议的项目将促进我们对中风痉挛的神经生物学基础的理解，提出 新的定量神经影像学标记物，以准确预测痉挛并发症，并提供结果 评估哪些治疗方法最直接针对痉挛的神经起源的措施。

项目成果

FASB: an integrated processing pipeline for Functional Analysis of simultaneous Spinal cord-Brain fMRI.

FASB：用于同步脊髓-脑功能磁共振成像功能分析的集成处理流程。

• DOI: 10.21203/rs.3.rs-3889284/v1
• 发表时间: 2024
• 期刊: Research square
• 作者: Vahdat,Shahabeddin;Landelle,Caroline;Lungu,Ovidiu;DeLeener,Benjamin;Doyon,Julien;Baniasad,Fatemeh
• 通讯作者: Baniasad,Fatemeh