Locating the neural substrates for the flexor synergy after stroke

中风通常会损害大脑的运动区。可以理解的是，这会导致行动不便 控制：四肢无力，动作较慢，协调性较差。除了损失 功能，患者还获得不必要的肌肉收缩称为协同作用。例如，每当手臂处于 抬起(肩部外展)，肘部屈曲。这些协同收缩干扰了正常的动作。协同效应， 不仅是虚弱或缺乏控制力，也是中风幸存者残疾的主要原因。许多以前的研究 我研究了动物(通常是猴子，因为它们的运动非常相似)中风的恢复 系统对人类)，但这些都侧重于功能丧失的恢复，而不是协同作用。一个原因是，在 大多数以前的工作猴子并没有表现出明显的协同效应；因此，到目前为止，我们还缺乏一个模型 中风后残疾的主要原因之一。我们在理解上的这一关键差距基本上已经消失了 没人注意到。我们需要知道如何在猴子身上诱导协同效应，哪些神经回路对它们负责， 他们是如何在健康状态下被控制的，以及这种控制是如何在中风后变得混乱的。这一项目旨在 解决这一差距，为采取合理的方法实现协同增效铺平道路。 在第一个实验中，猴子将接受到达任务的训练，然后植入电极以 测量肌肉活动。高速录像将提取运动运动学。仪表式直线器 马达将测量肌腱敲击反射。在基线记录后，我们将诱发局灶性皮质缺血损伤， 并在接下来的几个月里收集进一步的数据。我们将衡量不适当的发展 向外伸展时肘屈肌与肩部外展肌的收缩。我们将分析到达 量化运动质量的轨迹(相当于手部的灵巧度，但伸展范围)。肌腱 轻拍反射将评估痉挛状态。将对五个不同皮质区域的损伤进行比较。损伤是指 产生最严重的协同作用，然后与大细胞红核的损害结合在一起，这 我们假设将进一步强调协同表达。这项实验将阐明详细的功能 对中风后综合征的解剖，也产生了病理协同作用的优化猴子模型。 在第二个实验中，猴子将被训练移动肩部控制的屏幕上的光标 外展-肘部屈曲扭矩进入目标，允许参数检查独立和联合 激活。最初，神经回路将在健康的猴子身上表现出来。在必要的外科植入物之后， 神经活动将被记录在运动皮质、网状结构和脊髓的不同部分。 电源线。我们假设脊髓环路将显示出与肩部和肩部共同激活相一致的神经活动 肘部肌肉产生协同作用；脊柱上区域的活动将与推动这一脊柱 循环，或抑制它以允许独立的肌肉激活。然后在猴子身上重复录音 使病变产生最佳的协同效应，揭示病变的本质。

A stroke often damages motor areas of the brain. Understandably, this leads to a loss of movement control: the limbs become weak, and movements are slower and less well-coordinated. In addition to loss of function, patients also gain unwanted muscle contractions called synergies. For example, whenever the arm is lifted (shoulder abduction), the elbow flexes. These co-contractions intrude into normal movements. Synergies, not just weakness or lack of control, are a major contributor to disability in stroke survivors. Many previous studies have investigated stroke recovery in animals (typically monkeys because of the close similarities of their motor system to humans), but these have focused on recovery of lost function, not on synergies. One reason is that in most previous work monkeys did not express overt synergies; until now we have therefore lacked a model of one of the major causes of post-stroke disability. This critical gap in our understanding has largely gone unnoticed. We need to know how to induce synergies in monkeys, which neural circuits are responsible for them, how they are controlled in health, and how this control becomes disordered after stroke. This project seeks to address this gap, paving the way for a rational approach to new therapy for synergies. In the first experiment, monkeys will be trained on a reaching task, and then implanted with electrodes to measure muscle activity. High speed video recordings will extract movement kinematics. An instrumented linear motor will measure tendon-tap reflexes. After baseline recordings, we will induce a focal cortical ischemic lesion, and gather further data over the subsequent months. We will measure the development of inappropriate contractions of elbow flexors with shoulder abductors during outward reaches. We will analyze reaching trajectories to quantify quality of movement (equivalent to a dexterity measure in the hand, but for reach). Tendon tap reflexes will assess spasticity. Lesions of five different cortical regions will be compared. The lesion which produces the most severe synergy will then be combined with damage to the magnocellular red nucleus, which we hypothesize will further accentuate synergy expression. This experiment will elucidate the detailed functional anatomy of the post-stroke syndrome, and also yield an optimized monkey model of pathological synergies. In the second experiment, monkeys will be trained to move an on-screen cursor controlled by shoulder abduction-elbow flexion torques into targets, allowing parametric examination of independent versus co- activation. Initially neural circuits will be characterized in healthy monkeys. After necessary surgical implants, neural activity will be recorded from different parts of the motor cortex, the reticular formation, and the spinal cord. We hypothesize that spinal circuits will show neural activity consistent with co-activation of shoulder and elbow muscles to generate synergies; activity in supraspinal areas will be consistent with either driving this spinal circuit, or suppressing it to allow independent muscle activation. Recordings will then be repeated in monkeys subjected to the lesion which generates optimal synergies, to reveal the nature of pathological changes.