Faculty of Medical Sciences, Institute of Neuroscience, Newcastle University Newcastle Upon Tyne, UK ; Donoghue Lab, Department of Neuroscience, Brown University Providence, RI, USA.
Faculty of Medical Sciences, Institute of Neuroscience, Newcastle University Newcastle Upon Tyne, UK.
Front Neurosci. 2014 May 19;8:87. doi: 10.3389/fnins.2014.00087. eCollection 2014.
As yet, no cure exists for upper-limb paralysis resulting from the damage to motor pathways after spinal cord injury or stroke. Recently, neural activity from the motor cortex of paralyzed individuals has been used to control the movements of a robot arm but restoring function to patients' actual limbs remains a considerable challenge. Previously we have shown that electrical stimulation of the cervical spinal cord in anesthetized monkeys can elicit functional upper-limb movements like reaching and grasping. Here we show that stimulation can be controlled using cortical activity in awake animals to bypass disruption of the corticospinal system, restoring their ability to perform a simple upper-limb task. Monkeys were trained to grasp and pull a spring-loaded handle. After temporary paralysis of the hand was induced by reversible inactivation of primary motor cortex using muscimol, grasp-related single-unit activity from the ventral premotor cortex was converted into stimulation patterns delivered in real-time to the cervical spinal gray matter. During periods of closed-loop stimulation, task-modulated electromyogram, movement amplitude, and task success rate were improved relative to interleaved control periods without stimulation. In some sessions, single motor unit activity from weakly active muscles was also used successfully to control stimulation. These results are the first use of a neural prosthesis to improve the hand function of primates after motor cortex disruption, and demonstrate the potential for closed-loop cortical control of spinal cord stimulation to reanimate paralyzed limbs.
目前,对于脊髓损伤或中风导致运动通路受损而引起的上肢瘫痪,还没有治愈方法。最近,瘫痪个体的运动皮层神经活动已被用于控制机器人手臂的运动,但要恢复患者实际肢体的功能仍然是一个巨大的挑战。我们之前曾表明,在麻醉猴子的颈脊髓中进行电刺激可以诱发类似于伸手和抓握的功能性上肢运动。在这里,我们展示了可以使用皮层活动在清醒动物中进行控制,从而绕过皮质脊髓系统的中断,恢复它们执行简单上肢任务的能力。猴子被训练去抓握和拉动一个带弹簧的手柄。在手因使用 muscimol 可逆性失活初级运动皮层而暂时瘫痪后,来自腹侧前运动皮层的与抓握相关的单个单元活动被转换为实时传递到颈脊髓灰质的刺激模式。在闭环刺激期间,与没有刺激的交迭控制期相比,任务调制的肌电图、运动幅度和任务成功率得到了改善。在一些会话中,还成功地使用来自弱活动肌肉的单个运动单元活动来控制刺激。这些结果是首次使用神经假体在运动皮层破坏后改善灵长类动物的手部功能,并证明了闭环皮层控制脊髓刺激使瘫痪肢体恢复活力的潜力。