PLASTICITY OF HUMAN SPINAL NEURAL NETWORKS AFTER INJURY

人类脊髓神经网络受伤后的可塑性

• 批准号: 7724333
• 负责人: SUSAN J HARKEMA
• 金额: $ 0.26万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724333
• 关键词: Adverse effects; Bilateral; Biological Neural Networks; Clonus; Computer Retrieval of Information on Scientific Projects Database; Contralateral; Cues; Electromyography; Flexor; Frequencies; Funding; Grant; Human; Individual; Injury; Institution; Interneurons; Invasive; Ipsilateral; Learning; Leg; Manuals; Motor; Motor output; Output; Pattern; Pharmaceutical Preparations; Physiological; Recovery of Function; Reporting; Research; Research Personnel; Resources; Sensory; Source; Spinal; Spinal Cord; Spinal cord injury; Step training; Stimulus; Stretching; Training; United States National Institutes of Health; Walking; improved; neural circuit; relating to nervous system; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. "Clonus is one manifestation of spasticity, and produces involuntary neuromuscular responses that can interfere with the ability to walk after spinal cord injury (SCI). Clonus results in oscillatory efferent output generated by repetitive afferent input and the activation of central neural oscillators. The frequency of clonus is similar when driven by different types of repetitive afferent stimuli such as during standing and stepping. Clonus can radiate across several spinal cord segments and the oscillatory efferent output is modulated by interneurons. Thus, clonus can be used as a physiological probe to understand the functional organization of interneuronal circuits. We propose to study clonus during manual stretch of the plantarflexors, standing, and stepping to assess whether repetitive afferent input can alter the functional interneuronal organization of the human spinal cord. We will assess whether the specific afferent input related to loading modulates the central oscillators that generate clonus to modify efferent output after severe SCI. We hypothesize that manual stretch of the plantarflexors, standing and stepping will result in different co-activation patterns of clonic EMG among ipsilateral and contralateral flexors and extensors. Also, if a higher level of load to the legs is provided during standing and stepping, the clonic EMG activity will be reduced with an increase in tonic activity of bilateral flexors and extensors. We have observed that when individuals after severe spinal cord injury undergo multiple stand or step training sessions clonus and spasticity are reduced. We propose that intensive training that provides specific sensory information related to loading can reconfigure spinal networks to modify and reduce clonus after severe SCI. We suggest that the repetitive afferent input related to loading induces significant and persistent functional reorganization of interneuronal circuits. We hypothesize that after intensive training the same afferent input will alter clonic EMG activity. The proposed studies will further our understanding of the mechanisms of clonus after severe SCI. Further, we will learn whether the spinal neural networks responsible for clonus interact with those that generate standing and stepping. We will also understand whether the repetitive presentation of specific sensory information by training can reconfigure spinal neural networks to generate more functional motor output. Clonus is routinely treated with drugs, or even invasive strategies, with the intent to diminish clonus to enhance motor function. Unfortunately, side effects, rebound spasticity and limited recovery of function are often reported. We suggest that anti-spasticity medication may actually be interfering with the neural circuits needed for standing and walking. If this is the case, then specific training that uses task appropriate sensory cues for standing and walking may alleviate clonus and spasticity, reduce the need for medication, and improve motor function in individuals with severe SCI.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 “阵挛是痉挛的一种表现，并产生不自主的神经肌肉反应，可干扰脊髓损伤（SCI）后的行走能力。阵挛导致由重复传入输入和中枢神经振荡器的激活产生的振荡传出输出。当由不同类型的重复传入刺激驱动时，阵挛的频率是相似的，例如在站立和踏步期间。阵挛可以辐射到多个脊髓节段，振荡传出输出受中间神经元的调制。因此，阵挛可以作为一种生理学探针来了解神经元间回路的功能组织。我们建议研究阵挛期间手动伸展的跖屈肌，站立，步进，以评估是否重复传入输入可以改变人类脊髓的功能interneuronal组织。我们将评估与负荷相关的特定传入输入是否调节了产生阵挛的中枢振荡器，以修改严重SCI后的传出输出。我们假设，手动伸展跖屈肌，站立和踏步将导致不同的共激活模式的阵挛性肌电图同侧和对侧屈肌和伸肌。此外，如果在站立和踏步期间向腿部提供更高水平的负荷，则阵挛性EMG活动将随着双侧屈肌和伸肌的紧张性活动的增加而减少。我们已经观察到，当严重脊髓损伤后的个体经历多次站立或踏步训练时，阵挛和痉挛会减少。我们建议，强化训练，提供特定的感觉信息有关的负荷可以重新配置脊髓网络，以修改和减少严重SCI后阵挛。我们认为，与负荷相关的重复传入输入诱导显著和持久的神经元间回路的功能重组。我们假设，在密集的训练后，相同的传入输入将改变阵挛性肌电图活动。这些研究将进一步加深我们对严重脊髓损伤后阵挛发生机制的认识。此外，我们将了解负责阵挛的脊髓神经网络是否与产生站立和踏步的脊髓神经网络相互作用。我们还将了解通过训练重复呈现特定感觉信息是否可以重新配置脊髓神经网络，以产生更多功能性运动输出。阵挛通常用药物治疗，甚至是侵入性策略，目的是减少阵挛以增强运动功能。不幸的是，副作用，反弹痉挛和有限的功能恢复经常报告。我们认为，抗痉挛药物实际上可能会干扰站立和行走所需的神经回路。如果是这种情况，那么使用任务适当的站立和行走感觉线索的特定训练可能会减轻阵挛和痉挛，减少对药物的需求，并改善严重SCI患者的运动功能。