Enhancement of Motor Cortex Activity in Persons with Spinal Cord Injury

描述(由申请人提供)： 在美国估计有225,000-296,000名脊髓损伤和/或疾病(SCI&D)患者中，超过25,000人通过退伍军人管理局医疗保健系统接受护理。皮质脊髓通路的中断会导致病变水平以下的肌肉活动受损。对于颈部水平损伤的人，抓握和操纵物体的能力会丧失或减弱，影响独立性和社会参与。最近一项对347名四肢瘫痪患者的调查表明，手和手臂功能的恢复是与功能恢复有关的首要任务。慢性脊髓损伤的病理生理学可能限制甚至阻止传统疗法的功能改善，促进脊髓再生和通过备用神经通路最大化功能的新疗法的需求。慢性瘫痪导致大脑功能重组，减少了固定肢体的神经能力，进一步挑战了功能的恢复。因此，改善脊髓损伤后功能的关键是开发新的治疗方法，直接影响大脑和脊髓中神经元的功能，并采用促进功能恢复所需的神经可塑性机制。神经可塑性起着关键作用，因为它使神经系统能够适应，加强备用的皮质脊髓连接。我们的目标是开发一种新的脑机接口神经反馈范式，结合生物反馈、运动想象、动作观察和模仿的优势，促进四肢瘫痪退伍军人的运动皮质激活。通过直接针对神经元活动，我们的目标是促进神经可塑性，通过增加皮质活动幅度和自愿控制皮质调节来衡量。在这项研究中，我们将使用脑磁图(MEG)测量患有四肢瘫痪的退伍军人和正常对照组在观察到的、想象的、模拟的和公开的上肢运动中的皮质激活。这一基线评估使我们能够比较四肢瘫痪患者和一组健全受试者在简单运动任务中的皮质激活情况。我们将重点关注两个动作，一个是四肢瘫痪患者由于完全瘫痪而无法明显表现出来的动作，另一个是由于部分瘫痪而受限的动作。对于因完全瘫痪而受损的动作，受试者想象与实验者进行动作的视频一起进行动作(动作观察)。对于有残留功能的动作，受试者将在视觉反馈(动作模仿)的同时，尽其所能地执行该动作。在训练活动、动作观察和模仿中展示的视频与镜像神经系统接触，镜像神经系统是运动皮质兴奋性的有力促进器。一旦我们确定了四肢瘫痪受试者中负责预期运动的皮质区域，我们将使用脑磁图通过将虚拟手显示的动作与脑磁图信号实时调制相结合来提供神经反馈。与生物反馈类似，生理信号被用来影响行为，在这种情况下，是皮质调节。通过将脑磁图信号耦合到虚拟手，我们激活了镜像神经系统，该系统将观察到的动作映射到受试者自己的运动表示上。我们相信，这种神经反馈训练模式可以用来加强通向受损上肢的皮质脊髓通路，从而改善皮质脊髓通路部分完整的肌肉的功能(增加力量)。结合脑机接口技术或脊髓再生，当失去自主控制时，增强皮质激活可能会增强运动控制。

DESCRIPTION (provided by applicant): Of the estimated 225,000-296,000 people in the United States with a spinal cord injury and/or disorder (SCI&D), more than 25,000 receive care through the VA health care system. Disruption of corticospinal pathways results in impaired muscle activation below the level of the lesion. For individuals with cervical level injuries, the ability to grasp and manipulate objects is lost or diminished, impacting independence and social participation. A recent survey of 347 individuals with tetraplegia identified restoration of hand and arm function as the top priority related to functional recovery. The pathophysiology of chronic SCI may limit or even prevent functional improvement through traditional therapies, fostering the need for new treatments that promote spinal cord regeneration and maximize function through spared neural pathways. Chronic paralysis leads to functional reorganization in the brain, reducing the neural capacity available to immobilized limbs, further challenging recovery of function. Therefore, a key to improving function after SCI is to develop new therapies that directly influence the function of neurons in the brain and spinal cord and engage the mechanisms of neuroplasticity needed to facilitate recovery of function. Neuroplasticity plays a critical role as it enables the nervous system to adapt, strengthening spared corticospinal connections. We aim to develop a novel BCI neurofeedback paradigm that combines the advantages of biofeedback, motor imagery, and action observation and imitation to facilitate motor cortex activation in veterans with tetraplegia. By directly targeting neuronal activity, we aim to facilitate neuroplasticity measured as increased cortical activity amplitude and voluntary control over cortical modulation. In this study we will measure cortical activation using magnetoencephalography (MEG) during observed, imagined, imitated, and overt upper limb movements in veterans with tetraplegia and an unimpaired control group. This baseline evaluation allows us to compare cortical activation during simple movement tasks between individuals with tetraplegia and in a group of able-bodied subjects. We will focus on two movements, one that subjects with tetraplegia cannot perform overtly due to complete paralysis and a second movement limited by partial paralysis. For the movement impaired by complete paralysis, subjects imagine performing the movement along with a video of an experimenter performing the action (action observation). For the movement with residual function, subjects will perform the movement to their best ability along with the visual feedback (action imitation). The video displayed in both training activities, action observation, and imitation, engages the mirror neuron system, which is a potent facilitator of motor cortex excitability. Once we identify the cortical areas responsible for intended movement in subjects with tetraplegia, we will use MEG to provide neurofeedback by coupling the action of a virtual hand display to MEG signal modulation in real-time. Similar to biofeedback, a physiological signal is being used to influence behavior, in this case cortical modulation. By coupling the MEG signals to a virtual hand, we activate the mirror neuron system which will map the observed action onto the subject's own motor representation. We believe that this neurofeedback training paradigm can be used to strengthen corticospinal pathways to the impaired upper limb, thus improving function (increased strength) in muscles with partially intact corticospinal pathways. In combination with BCI technology or spinal cord regeneration, enhancing cortical activation may augment motor control when voluntary control has been lost.