Neuroplasticity induced by functional electrical stimulation

由于神经疾病或损伤(如脊髓损伤或中风)导致肌肉瘫痪的人的站立和行走功能受损，严重限制了他们进行日常生活活动的能力，并降低了他们的生活质量。功能性电刺激是一种利用电刺激来人工激活瘫痪肢体肌肉的方法，可以改善患者的患肢功能。例如，当瘫痪手臂的人需要握住咖啡杯时，紧闭手指的肌肉会受到刺激，产生抓握运动。这是一种恢复功能性动作的有效方法，但它实际上很难应用于日常生活活动中所需的许多复杂动作。人们发现，重复使用功能性电刺激会导致大脑和/或脊髓中神经回路的永久性变化，即所谓的神经可塑性。这一发现可能对神经康复产生巨大影响，但利用功能性电刺激诱导神经可塑性的神经机制和有效途径尚不完全清楚。功能性电刺激诱导神经可塑性的一个可能机制是脊髓的突触加强。当来自大脑的指令和在运动神经上反向传播的电刺激产生的信号在脊髓相遇时，大脑和肌肉之间的突触连接的强度会增加(即来自大脑的指令传递到肌肉的效率)。重复这个过程会永久加强大脑和肌肉之间的连接，这可以增加肌肉力量，改善肢体运动。这项拟议的研究计划旨在探索功能性电刺激可以促进人类运动控制系统中神经可塑性的有效方法，重点是脊髓的突触加强，即脊髓正在发生的事情。对于这种机制，需要两个神经信号：一个来自大脑，另一个来自周围神经。来自大脑的信号可以简单地通过患者的自愿努力来诱导(即，如果患者想要移动肢体，来自大脑的命令将传递到肌肉)。另一种从大脑发出信号的方法是使用经颅磁刺激。通过刺激负责肢体瞬间的大脑皮质区域，经颅磁刺激激活负责的神经元，神经元向肌肉发送命令。有四种方式可以产生来自周围神经的神经信号：1)在到达目标肌肉的神经通路处刺激感觉神经干，2)刺激目标肌肉内的神经末梢，3)刺激脊髓中的运动神经元，4)在神经通路到目标肌肉的神经通路处刺激运动神经干。通过适当地结合脑神经信号和来自周围神经的神经信号，可以假设在脊髓可以诱导神经可塑性。在这个项目中，我将系统地测试每种组合，以研究和开发最有效的方式来传递功能性电刺激，以诱导大脑和肌肉之间的突触加强。最终，该项目将开发一种神经工程学方法的基础，该方法可以帮助肌肉瘫痪的人恢复失去的运动，这将不可避免地导致生活质量的提高。

Compromised standing and walking function among people who have paralyzed muscles due to a neurological disease or injury, such as spinal cord injury or stroke, critically limits their ability to perform activities of daily living, and reduces their quality of life. Functional electrical stimulation, which is a method that can artificially activate muscles in the paralyzed limbs by use of electrical stimulation, can lead to improvement of patient’s affected limb function. For example, when a person with a paralyzed arm needs to grasp a coffee cup, muscles that close fingers are stimulated to produce a grasping movement. This is an effective way to regain functional movements, but it is practically difficult to apply to many complex movements which are required during activities of daily living. It was discovered that repetitive use of functional electrical stimulation can cause permanent changes of the neural circuits in the brain and/or the spinal cord, which is the so-called neuroplasticity. This discovery could have tremendous impacts in neurorehabiliation but the neural mechanisms and the effective ways of using functional electrical stimulation to induce the neuroplasticity are not fully understood. One probable mechanism behind the neuroplasticity induced by functional electrical stimulation is the synaptic strengthening at the spinal cord. When a command from brain and the signal caused by electrical stimulation which is traveling backward on the motor nerve meet at spinal cord, the strength of the synaptic connection between the brain and the muscle increases (i.e., how effectively the command from brain travels to muscle). Repeating this process leads to permanent strengthening of the connection between the brain and the muscle, which can increase the muscle force and improve limb movement. The proposed research program aims to explore the effective ways that functional electrical stimulation can facilitate neuroplasticity in the human motor control system, focusing on this synaptic strengthening at the spinal cord, i.e., what is happening in the spinal cord. For this mechanism, two neural signals are required: One from the brain and the other from peripheral nerves. A signal from the brain can be induced simply by the patient’s voluntary effort (i.e., if patient want to move a limb, a command from brain will travel to the muscle). The other way to cause a signal from the brain is to use transcranial magnetic stimulation. By stimulating the cortical area of the brain responsible for the limb moment, transcranial magnetic stimulation activates the responsible neurons and the neurons send a command to the muscle. There are four ways to cause the neural signal from peripheral nerves; 1) to stimulate the sensory nerve trunk at a nerve pass to the target muscle, 2) to stimulate the nerve ending within the target muscle, 3) to stimulate the motor neurons in the spinal cord, 4) to stimulate the motor nerve trunk at a nerve pass to the target muscle. By appropriately combining the brain neural signal and neural signal from peripheral nerves, it is hypothesized that neuroplasticity can be induced at the spinal cord. In this program, I will test each combination systematically to investigate and develop the most effective way to deliver functional electrical stimulation to induce the synaptic strengthening between the brain and the muscle. At the end, this program will develop a basis of a neuroengineering method which can help people with paralyzed muscles regain their lost movements, which will inevitably lead to increased quality of life.