Locating the neural substrates for the flexor synergy after stroke

定位中风后屈肌协同作用的神经基质

• 批准号: 10095850
• 负责人: Stuart N Baker
• 金额: $ 46.01万
• 依托单位: UNIVERSITY OF NEWCASTLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10095850
• 关键词: Address; Anatomy; Animals; Anterior; Area; Automobile Driving; Basal Ganglia; Brain; Cells; Corticospinal Tracts; Data; Deep Brain Stimulation; Development; Disease; Dorsal; Drug usage; Elbow; Electrodes; Face; Flexor; Hand; Health; Human; Impairment; Implant; Laboratories; Lead; Learning; Left; Lesion; Lifting; Limb structure; Macaca; Measurement; Measures; Methods; Modeling; Monkeys; Motor; Motor Cortex; Motor Neurons; Movement; Muscle; Muscle Contraction; Nature; Neurons; Operative Surgical Procedures; Outpatients; Parkinson Disease; Pathologic; Pathway interactions; Patients; Pharmaceutical Preparations; Physical therapy; Physiological; Primates; Recovery; Red nucleus structure; Reflex action; Reticular Formation; Shoulder; Speed; Spinal; Spinal Cord; Stroke; Syndrome; System; Task Performances; Tendon structure; Tennis; Therapeutic Intervention; Time; Torque; Training; Upper Extremity; Video Recording; Work; arm; dexterity; disability; experimental study; improved; instrument; ischemic lesion; kinematics; loss of function; magnocellular; neural circuit; neural stimulation; novel; novel therapeutics; post stroke; prevent; programs; relating to nervous system; spasticity; stroke recovery; stroke survivor; synergism

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.

中风通常会损害大脑的运动区。可以理解的是，这导致了运动的损失 控制：四肢无力，动作迟缓，协调性差。除了损失 功能，患者也获得不必要的肌肉收缩称为协同作用。例如，每当手臂 抬起（肩外展），手肘弯曲。这些共同收缩干扰了正常的运动。协同增效， 不仅仅是虚弱或缺乏控制，是中风幸存者残疾的主要原因。许多既往研究 已经研究了动物（通常是猴子，因为它们的运动非常相似 这些方案侧重于恢复丧失的功能，而不是协同增效。一个原因是， 大多数以前的工作猴子没有表现出明显的协同作用;因此，到目前为止，我们缺乏一个模型， 中风后残疾的主要原因之一。我们认识上的这一关键差距在很大程度上已经消失 因未得到人们注意我们需要知道如何在猴子身上诱导协同作用，哪些神经回路负责它们， 它们在健康状态下是如何被控制的，以及这种控制在中风后是如何变得紊乱的。本项目谋求 解决这一差距，为合理开发新的协同疗法铺平道路。 在第一个实验中，猴子将接受一项伸手任务的训练，然后植入电极， 测量肌肉活动。高速视频记录将提取运动学。一种仪表化线性 马达会测量腱反射。在基线记录后，我们将诱导局灶性皮质缺血性损伤， 并在接下来的几个月里收集更多的数据。我们将衡量不适当的发展 肘屈肌与肩外展肌在向外伸展时的收缩。我们将分析达到 轨迹来量化运动的质量（相当于手部的灵巧性测量，但用于达到）。肌腱 敲击反射可以评估痉挛状态将比较五个不同皮质区域的病变。的病灶 产生最严重的协同作用，然后将与大细胞红核的损伤结合起来， 我们假设将进一步加强协同表达。这个实验将阐明详细的功能 解剖中风后综合征，也产生一个优化的猴子模型的病理协同作用。 在第二个实验中，猴子将被训练移动由肩膀控制的屏幕光标 外展肘关节屈曲扭矩进入目标，允许参数检查独立与共同 activation.最初，神经回路将在健康的猴子中进行表征。经过必要的手术植入后， 将从运动皮层、网状结构和脊髓的不同部分记录神经活动。 线.我们假设，脊髓回路将显示与肩部和肩部共同激活一致的神经活动。 肘部肌肉产生协同作用;在脊髓上区域的活动将与驱动这个脊柱 回路，或抑制它以允许独立的肌肉激活。然后在猴子身上重复记录 受到病变产生最佳协同作用，揭示病变的本质。