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理解上层神经底层机制的关键知识差距 肢体中风后痉挛，通过直接评估下行运动和上行感觉通路 手部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，阻碍上肢功能恢复，并引起并发症，例如 其传统特征是肌肉的速度依赖性增加。 张力（张力亢进）和脊髓牵张反射增加（反射亢进）虽然是外周和脊髓的。 主要研究了痉挛的特征、其潜在的大脑机制和脑脊髓 途径仍然存在争议，这种理解对于解决当前的局限性至关重要。 痉挛的临床治疗与其早期诊断、预后因素的识别以及缺乏 针对损伤的根源而不是其症状的有效治疗。 研究表明，包括网状脊髓束（RST）在内的下行运动通路的病变可能导致痉挛 相反，中风后脊髓感觉运动回路和上行感觉发生变化。 预测可能是中风后反射亢进的基础，但尚不清楚中风后的大脑损伤如何导致这些症状。 脊髓回路的远程变化。早期电生理学工作支持的几种理论模型。 在猫中，表明背侧和内侧 RST 的抑制性和兴奋性投射不平衡 然而，灵长类动物的新证据表明 RST 预测的类型。 （抑制性/兴奋性）不遵循当前痉挛模型中假设的背侧/内侧组织， 但取决于预测的偏侧性，在这个提案中，我们的目标是将这些新发现转化为人类， 并检查它们与中风后痉挛的相关性。我们的中心假设是，在中风幸存者中。 痉挛，同侧与对侧 RST 激活不平衡与痉挛性肌张力增高直接相关， 而背柱体感投射的过度活跃与痉挛性反射亢进有关。 根据这一假设，我们将采用一种强大的神经成像方法，使用同步脊髓-大脑 功能性磁共振成像（fMRI）在慢性偏瘫性卒中患者（伴或不伴上肢）中的应用 肢体痉挛以及健康对照使用这种方法，我们将评估主要下降的功能。 （皮质脊髓，RST）和上升（背柱，前外侧束）通路在手部运动和 我们将确定这些神经影像标记与痉挛性肌张力增高之间的关系。 反射亢进，通过可靠的生物力学和电生理学测量进行评估。 拟议的项目将增进我们对中风后痉挛的神经生物学基础的理解，提供 新的定量神经影像标记物可准确预测痉挛并发症，并提供结果 评估哪些治疗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