PLASTICITY OF HUMAN SPINAL NEURAL NETWORKS AFTER INJURY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Clonus是痉挛的一种表现，会产生不自主的神经肌肉反应，干扰脊髓损伤（SCI）后的行走能力。Clonus的结果是由重复传入输入和中枢神经振荡器的激活所产生的振荡输出。当受到不同类型的重复传入刺激时，如站立和行走时，耳鸣的频率相似。Clonus可以辐射到多个脊髓节段，振荡输出由中间神经元调节。因此，克隆可以作为一种生理探针来了解神经元间回路的功能组织。我们建议通过研究跖屈肌的手动伸展、站立和行走时的clonus来评估重复性传入输入是否会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会调节产生克隆的中央振荡器，从而改变严重脊髓损伤后的传出输出。我们假设手动拉伸跖屈肌、站立和行走将导致同侧和对侧屈伸肌之间不同的阵挛肌电图共激活模式。此外，如果在站立和行走时腿部承受更高水平的负荷，阵挛性肌电活动将随着双侧屈肌和伸肌强直活动的增加而减少。我们观察到，当严重脊髓损伤后的个体进行多次站立或踏步训练时，阵挛和痉挛会减少。我们认为，强化训练提供了与负荷相关的特定感觉信息，可以重新配置脊髓网络，以改变和减少严重脊髓损伤后的冠状肌。我们认为，与负荷相关的重复性传入输入诱导了神经元间回路的显著和持续的功能重组。我们假设在高强度训练后，相同的传入输入会改变阵挛肌电活动。本研究将进一步加深我们对严重脊髓损伤后冠状突发生机制的认识。此外，我们将了解是否脊髓神经网络负责clonus与那些产生站立和行走相互作用。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。Clonus的常规治疗是药物治疗，甚至是侵入性治疗，目的是减少Clonus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被报道。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感觉提示进行站立和行走的特定训练可能会减轻严重脊髓损伤患者的阵挛和痉挛，减少对药物的需求，并改善运动功能。

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.