Biomedical Engineering IDP, University of California, Los Angeles, CA 90095, USA.
J Neuroeng Rehabil. 2013 Jan 21;10:2. doi: 10.1186/1743-0003-10-2.
Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array.
We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats.
In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia.
Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.
刺激脊髓已被证明具有很大的潜力,可以改善因损伤或病理状况引起的运动功能障碍。通过使用广泛的动物模型,许多研究表明,刺激脊髓内在神经网络可以显著改善运动能力,甚至可以使完全脊髓横断的动物能够行走和站立。然而,由于植入程序的侵入性、传统刺激技术的多功能性不足以及确定能够提供运动缺陷最佳改善的刺激特定部位的困难,该技术的临床应用一直发展缓慢。此外,用于通过生物相容电极长期控制精确刺激的工具的开发也受到限制。在本文中,我们概述了该技术的发展及其在脊髓大鼠模型中的应用,展示了使用该阵列识别和刺激脊髓特定部位以产生脊髓大鼠离散运动行为的能力。
我们设计了一种可慢性植入、快速切换、高密度基于铂的多电极阵列,可用于在单极和双极配置下以 1-100 Hz 和 1-10 V 的频率刺激,以检查完全脊髓横断大鼠脊髓硬膜外刺激的电生理和行为影响。
在本文中,我们证明了在改善脊髓损伤后运动恢复方面使用高分辨率刺激参数的有效性。我们观察到,当特定的电极组被持续刺激(40 Hz)时,瘫痪后肢的大鼠可以站立和行走。通过刺激阵列上位于特定脊髓水平的不同电极组合,并通过特定的刺激参数(即刺激频率和强度以及阴极/阳极方向),产生了不同的行走和站立模式。该阵列还用于通过在没有任何麻醉的情况下以 1 Hz 刺激诱导的诱发电位来评估脊髓背侧到中间神经元回路和特定运动池之间的功能连接。
因此,高密度电极阵列允许高空间分辨率和选择性激活脊髓腰骶区不同神经通路的能力,以促进成年脊髓大鼠的站立和行走,并提供引发运动电位的能力,从而为评估感觉回路与特定运动池和肌肉之间的连接提供了一种手段。