Rascoe Avi, Sharma Pawan, Shah Prithvi K
Division of Rehabilitation Sciences, Department of Physical Therapy, School of Health Technology and Management, Stony Brook University, Stony Brook, NY, United States.
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY, United States.
Front Neurosci. 2018 Jul 23;12:472. doi: 10.3389/fnins.2018.00472. eCollection 2018.
Extensive pre-clinical and clinical experimentation has yielded data on the robustness and versatility of epidural stimulation (ES) strategies to activate spinal neural circuitry to produce functional benefits. Increasing studies are now reporting that closed-loop electrical stimulation delivery methods significantly enhance the neuromodulation effects of stimulation, to in turn, improve physiological outcomes of the intervention. No studies have yet explored the feasibility and usage of closed-loop systems to neuromodulate the cervical spinal cord using ES. We developed an activity-dependent system that utilizes electromyography (EMG) activity to trigger epidural stimulation (tES) of the cervical spinal cord in awake, freely moving rats. Experiments were performed on rats that were implanted with chronic forelimb EMG and cervical epidural implants, with ( = 7) and without ( = 2) a complete C4 spinal hemisection. Our results show that the EMG triggered activity-dependent system can be reliably applied and reproduced for: (i) stimulating multiple rats simultaneously throughout the night during free home-cage activity and (ii) use as a mobile system for testing and training during various short-term behavioral testing conditions. The system was able to consistently generate stimulation pulse trains in response to attempted EMG activity that crossed a user-defined threshold in all rats for all experiments, including the overnight experiments that lasts for 7 h/session for 6 days/week through the 3-month period. The developed closed-loop system can be considered to represent a class of bidirectional neural prostheses via a circuit that enables two-way interactions between neural activity (real-time processing of EMG activity) and external devices (such as a stimulator). It can operate autonomously for extended periods of time in unrestrained rats, allowing its use as a long-term therapeutic tool. It can also enable us to study the long-term physiological effects of incorporating electrical stimulation techniques into the nervous system. The system can also be experimented for connecting several neural systems into a by combining neural signals from multiple rats dynamically and in real-time so as to enhance motor performance. Studies are ongoing in our laboratory to test the usefulness of this system in the recovery of hand function after cervical spinal cord injuries.
广泛的临床前和临床实验已经得出了关于硬膜外刺激（ES）策略激活脊髓神经回路以产生功能益处的稳健性和多功能性的数据。越来越多的研究报告称，闭环电刺激递送方法显著增强了刺激的神经调节效果，进而改善了干预的生理结果。尚未有研究探讨使用ES对颈脊髓进行神经调节的闭环系统的可行性和用途。我们开发了一种基于活动的系统，该系统利用肌电图（EMG）活动在清醒、自由活动的大鼠中触发颈脊髓的硬膜外刺激（tES）。对植入了慢性前肢EMG和颈硬膜外植入物的大鼠进行了实验，其中7只大鼠进行了完全C4脊髓半横断，2只大鼠未进行。我们的结果表明，EMG触发的基于活动的系统可以可靠地应用于并复制以下情况：（i）在自由笼内活动期间整夜同时刺激多只大鼠，以及（ii）在各种短期行为测试条件下用作测试和训练的移动系统。该系统能够在所有实验的所有大鼠中，响应超过用户定义阈值的尝试性EMG活动，持续产生刺激脉冲序列，包括为期3个月、每周6天、每次会话持续7小时的过夜实验。所开发的闭环系统可被视为通过一个电路代表一类双向神经假体，该电路能够实现神经活动（EMG活动的实时处理）与外部设备（如刺激器）之间的双向交互。它可以在不受约束的大鼠中长时间自主运行，允许其用作长期治疗工具。它还能使我们研究将电刺激技术纳入神经系统的长期生理效应。该系统还可以通过动态实时组合多只大鼠的神经信号，将多个神经系统连接成一个系统，以增强运动性能。我们实验室正在进行研究，以测试该系统在颈脊髓损伤后手功能恢复中的有用性。
