A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits
A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits
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DOI：
10.1523/jneurosci.1688-13.2013
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发表时间：
2013-12-04
影响因子：
5.3
通讯作者：
Micera, Silvestro
中科院分区：
文献类型：
--
作者：
Capogrosso, Marco;Wenger, Nikolaus;Micera, Silvestro
腰骶段的硬膜外电刺激（EES）可以恢复脊髓损伤后的运动范围。然而，EES促进运动执行的机制和神经结构仍不清楚。在这里，我们设计了一个计算模型，并进行了体内实验，以调查类型的纤维，神经元和电路招募响应EES。我们首先开发了一个真实的大鼠腰骶段有限元计算机模型，以识别EES产生的电流。为了评估这些电流对感觉运动回路的影响，我们将该模型与运动神经元、中间神经元和有髓传入纤维的解剖学上真实的轴突电缆模型相结合，用于拮抗性踝关节肌肉。计算机模拟和实验之间的比较表明，该模型能够预测多种强度和位置的EES诱发的运动反应。对募集的神经结构的分析显示，EES对运动神经元和中间神经元缺乏直接影响。模拟和药理学实验表明，EES通过募集有髓传入纤维跨突触连接脊髓回路。该模型还预测了空间上不同的EES调节侧特异性肢体运动的能力，以及在较小程度上的伸展与屈曲。这些预测在脊髓大鼠中通过EES实现站立和行走期间得到证实。这些综合结果为设计脊柱神经假体系统提供了一个机械框架，以改善神经系统疾病后的站立和行走。
Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders.