McPherson Jacob G, Miller Robert R, Perlmutter Steve I
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195.
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195
Proc Natl Acad Sci U S A. 2015 Sep 29;112(39):12193-8. doi: 10.1073/pnas.1505383112. Epub 2015 Sep 14.
Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural-computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury.
依赖于使用的运动疗法可使神经损伤后运动功能部分恢复。我们试图通过开发一种神经假体干预措施来改善恢复情况，该措施通过引导未受损运动通路中依赖于峰电位时间的可塑性来增强运动疗法。在患有脊髓颈段挫伤的大鼠中使用循环神经计算机接口，我们将损伤下方的脊髓内微刺激与受损前肢肌肉活动所发出的功能相关的自主运动指令的到达同步。在对前肢行为进行物理再训练期间以及全天持续3个月进行刺激。与接受靶向但开环脊髓刺激的动物以及仅接受物理再训练的大鼠相比，接受这种靶向的、依赖于活动的脊髓刺激（TADSS）的大鼠表现出明显增强的恢复。在前肢伸展和抓握任务中，接受TADSS的动物恢复了其损伤前能力的63%，是其他治疗组所达到的表现水平的两倍多。在没有刺激的情况下，治疗效果持续了另外3周。结果表明，依赖于活动的脊髓刺激可诱导神经可塑性，从而改善脊髓损伤后的行为恢复。
