Neuronal based prosthetic control of volitional movement

描述（由申请人提供）：无法沟通是中枢神经系统损伤最严重的致残方面之一，包括无法执行基本任务，如弯曲和伸展肢体或移动屏幕上的简单光标。到目前为止，大多数研究都是针对中枢神经系统受损区域（如脑干或颈近端脊髓）的内在修复或再生，而在功能完好的区域之间重定向信息的替代方法在很大程度上尚未探索。我们和其他人的研究表明，负责运动控制的皮层和皮层下区域的神经元活动可以准确地预测意志运动意图，并且在负责运动产生的区域传递与事件相关的电刺激可以重复地改变目标肢体运动。在当前的研究中，我们的目标是通过系统地匹配和改变灵长类动物在执行运动定向任务时的运动意图和运动产生来扩展这些发现。为此，我们将从相同的皮层下区域获得单神经元记录，以预测运动意图，并使用类似的系统设计向腹侧脊髓传递电刺激，以近似和改变运动产生。神经元活动的变化将在多个试验中进行检查，因为观察到的由神经元活动预测的运动与脊髓刺激产生的运动相对应或不匹配。这些发现将为运动神经元可塑性和脊髓传出活动在自适应运动控制中的个体作用提供一个独特的视角，并可能为旨在恢复意志运动的假肢设计的发展提供有价值的新见解。公共卫生相关性：运动缺陷是中枢神经系统受损的最令人衰弱的方面之一。尽管不断努力开发治疗此类损伤患者的方法，但仍然很少，通常没有可用于重建意志运动控制的选择。该项目旨在探索一种基于我们团队开发的用于清醒行为灵长类动物的系统设计的恢复运动通信的新方法。随着人工耳蜗、脑干和视网膜假体植入物的出现，这些设备的重大社会影响已经得到证明，并且可能同样为脑干和近端脊髓损伤导致的运动障碍患者提供显著的益处。

DESCRIPTION (provided by applicant): The inability to communicate underlies one of the most disabling aspects of injury to the central nervous system, and includes the inability to perform rudimentary tasks such as flexing and extending ones' limb or moving a simple cursor on a screen. While the majority of studies thus far have targeted the intrinsic repair or regeneration of damaged areas of the central nervous system such as brainstem or proximal cervical spinal cord, alternative approaches for redirecting information between areas that remain functionally intact is largely unexplored. Work by our group and others has demonstrated that neuronal activity in cortical and subcortical areas responsible for motor control can accurately predict volitional movement intention, and that delivery of event-related electrical stimuli in areas responsible for motor production can reproducibly alter targeted limb movement. In the current study, we aim to extend these findings by systematically matching and altering motor intent with movement production in primates performing a motor directional task. To this end, we will obtain single-neuronal recording from the same subcortical areas shown to predict motor intention and use a similar system design to deliver electrical stimuli to the ventral spinal cord in order to approximate and alter movement production. Changes in neuronal activity will be examined over multiple trials as observed movements predicted by neuronal activity are made to either correspond or mismatch movements produced by spinal cord stimulation. These findings will provide a unique perspective into the individual roles that motor neuronal plasticity and spinal efferent activity play in adaptive motor control, and may offer valuable new insight into the development of prosthetic designs aimed at restoring volitional movement. PUBLIC HEALTH RELEVANCE: Motor deficit is among the most debilitating aspects of subjects suffering injury to the central nervous system. Despite continued efforts to develop treatments for patients with such injury, there remain few and often no options available for reconstituting volitional motor control. The proposed project aims to explore a novel approach for restoring motor communication that is based on a system design developed by our group for use in awake-behaving primates. The significant social impact of such devices has already been demonstrated with the emergence of cochlear, brainstem and retinal prosthetic implants, and may similarly provide significant benefit for patients with motor disability resulting from brainstem and proximal spinal cord injury.