Optimizing peripheral stimulation parameters to modulate the sensorimotor cortex for post-stroke motor recovery

摘要 在美国，中风是导致残疾的主要原因，每年约有70万新病例 年。上肢功能障碍主要取决于手功能和手指的丧失 灵巧。尽管上肢的特定任务训练取得了进展，但大量的中风 患者不能完全恢复手的功能。躯体感觉周围神经刺激(PNS)是 中风患者手运动功能靶向恢复的一种有前景的方法。无论是短期还是 刺激周围神经后手功能的长期改善 在中风患者中表现出来。然而，并不是所有的研究都发现了一致的影响，也不是所有的 参与者体验到了显著的好处。改进也与以下方面的变化有关 中枢神经系统运动网络。然而，人们对PNS如何与PNS相互作用知之甚少 皮质神经生理学动力学。 需要系统地确定给药要求和作用机制 强健的临床翻译和慢性运动症患者的最大功能恢复 赤字。我们的建议旨在采取创新和全面的方法，让人类 受试者和卒中动物模型，以更好地靶向周围皮质动力学。重要的是，我们的 动物和人类中风受试者的初步数据表明，三叉神经痛和中风之间存在联系 静息状态下皮质动力学的变化。我们的建议是基于这样一个总体假设： 针对皮损周围皮质活动的滴定将提供一条更可靠的途径 为个人翻译和定制参数。使用受试者内研究设计和 运动学和神经生理学结果测量，我们建议进行研究，将描绘 如何修改和构建周围神经刺激，以最大限度地恢复功能。 我们目标的完成将为完善和有力地翻译提供必要的指导 周围神经调节对中风患者的影响。我们的研究将使我们能够：(1)明确和因果地 确定三叉神经节如何改变周围皮质活动和(2)确定两者之间的联系 皮损周围皮质活动调节和运动行为效应。我们期待着我们能够 开发一个计算模型，说明皮层活动如何通过持续的方式以渐进的方式进行修改 PNS。这可能允许我们开发针对正在进行的皮质的PNS的新方法 动态化和高度个性化，针对每个中风患者的特定损伤模式。

ABSTRACT Stroke is the leading cause of disability in the United States, with approximately 700,000 new cases per year. Disability from upper limb impairment depends primarily on loss of hand function and finger dexterity. Despite advances in task-specific training for the upper limb, a large number of stroke patients do not regain full function of their hand. Somatosensory peripheral nerve stimulation (PNS) is a promising approach to target recovery of hand motor function in stroke patients. Both short-term and long-term improvements in hand function after stimulation of the peripheral nerves have been demonstrated in stroke patients. However, not all studies have found consistent effects and not all participants have experienced significant benefits. Improvements have also been linked to changes in central nervous system motor networks. Very little is known, however, about how PNS interacts with cortical neurophysiological dynamics. A systematic determination of dosing requirements and mechanisms of action is required for robust clinical translation and for maximal functional restoration in those with chronic motor deficits. Our proposal aims to take an innovative and comprehensive approach involving both human subjects and an animal model of stroke to better target perilesional cortical dynamics. Importantly, our preliminary data in both animals and human stroke subjects demonstrates a link between PNS and changes in resting state cortical dynamics. Our proposal is based on the overall hypothesis that dose titration to specifically target perilesional cortical activity will offer a more robust path to reliable translation and customization of parameters to individuals. Using a within subject study design and kinematic and neurophysiological outcome measures, we propose to conduct studies that will delineate how to modify and structure peripheral nerve stimulation to maximize functional restoration. Completion of our aims will provide essential guidance for the refinement and robust translation of peripheral neuromodulation to stroke patients. Our studies will allow us to: (1) definitively and causally determine how perilesional cortical activity is modified by PNS and (2) determine the link between perilesional cortical activity modulation and motor behavioral effects. We anticipate that we can develop a computational model of how cortical activity is modified in a gradual manner by ongoing PNS. This may allow us to develop novel approaches to PNS that are tailored to ongoing cortical dynamics and highly individualized for each stroke patient's specific pattern of injury.