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: 7627689
• 负责人: SUSAN J HARKEMA
• 金额: $ 2.01万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627689
• 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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 阵挛是痉挛的一种表现，会产生不自主的神经肌肉反应，会干扰脊髓损伤(SCI)后的行走能力。阵挛导致由重复的传入输入和中枢神经振荡器激活而产生的振荡性传出输出。在不同类型的重复传入刺激的驱动下，如站立和行走时，阵挛的频率是相似的。阵挛可以辐射到多个脊髓节段，振荡性传出输出受到中间神经元的调节。因此，阵挛可以作为一种生理探针来了解神经元间回路的功能组织。我们建议研究在徒手伸展、站立和踏步时的阵挛，以评估重复的传入输入是否可以改变人类脊髓的功能性神经元间组织。我们将评估与负荷相关的特定传入输入是否调制产生阵挛的中央振荡器，以改变严重脊髓损伤后的传出输出。我们假设，徒手伸展、站立和行走将导致同侧和对侧屈肌和伸肌之间不同的阵挛肌电共同激活模式。此外，如果在站立和行走过程中给腿部提供较高水平的负荷，则随着双侧屈肌和伸肌的紧张性活动的增加，阵挛肌电活动会减少。我们已经观察到，当严重脊髓损伤后的个体接受多次站立或阶梯式训练时，阵挛和痉挛减少。我们认为，提供与负荷相关的特定感觉信息的强化训练可以重新配置脊髓网络，以修改和减少严重脊髓损伤后的阵挛。我们认为，与负荷相关的重复传入输入诱导了神经元间回路的显着和持续的功能重组。我们假设，在强化训练后，相同的传入输入会改变克隆性肌电活动。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理解。此外，我们还将了解负责阵挛的脊髓神经网络是否与产生站立和行走的神经网络相互作用。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，以产生更多功能运动输出。阵挛的治疗是常规的药物治疗，甚至是侵入性的治疗，目的是减少阵挛以增强运动功能。不幸的是，副作用、反弹痉挛和功能恢复受限是经常被报道的。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。如果是这样的话，使用适合任务的感觉线索站立和行走的特定训练可能会减轻阵挛和痉挛，减少对药物的需求，并改善严重脊髓损伤患者的运动功能。