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: 10371979
• 负责人: Stuart N Baker
• 金额: $ 45.77万
• 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/10371979
• 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; Persons; 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域。可以理解的是，这导致运动丧失 控制：四肢变得虚弱，运动较慢且协调较低。除了失去 功能，患者还会获得不必要的肌肉收缩，称为协同作用。例如，每当手臂是 抬起（肩部绑架），肘部弯曲。这些共同收缩侵入了正常运动。协同作用， 不仅是弱点或缺乏控制，还是中风幸存者残疾的主要贡献者。许多先前的研究 已经调查了动物的中风恢复（通常是由于其电动机的相似之处 对人类的系统），但这些集中在恢复损失功能，而不是协同上。原因之一是 以前的大多数工作猴子都没有表达明显的协同作用。因此，到目前为止，我们缺乏一个模型 冲程后残疾的主要原因之一。我们理解的这一关键差距已经大大消失了 未被注意。我们需要知道如何诱导猴子的协同作用，哪些神经回路负责它们， 它们如何控制健康，以及中风后这种控制如何变得无序。这个项目试图 解决这一差距，为合理的协同疗法铺平了道路。 在第一个实验中，猴子将接受到达到任务的训练，然后用电极植入到 测量肌肉活动。高速视频记录将提取运动运动学。仪器线性 电动机将测量肌腱-TAP反射。基线记录后，我们将引起局灶性皮质缺血病变， 并在随后的几个月中收集更多数据。我们将衡量不适当的发展 肘部屈肌在外部伸向侧面的肌力屈曲。我们将分析到达 量化运动质量的轨迹（相当于手中的敏捷度量，但要触及）。肌腱 TAP反射将评估痉挛。将比较五个不同皮质区域的病变。病变 然后，产生最严重的协同作用将与对大细胞红色核的损害结合，该核 我们假设将进一步强调协同表达。该实验将阐明详细的功能 中风后综合征的解剖结构，还产生了优化的病理协同模型。 在第二个实验中，将训练猴子移动由肩部控制的屏幕光标 绑架肘屈曲扭矩符合目标，从而允许对独立与共同的参数检查 激活。最初，神经回路将在健康的猴子中表征。经过必要的手术植入物后， 神经活动将从运动皮层的不同部分，网状形成和脊柱记录 绳索。我们假设脊柱电路将显示与肩膀共同激活一致的神经活动 肘部肌肉产生协同作用；脊柱上区域的活动将与驱动此脊柱一致 电路或抑制它以允许独立的肌肉激活。然后将在猴子中重复录音 受到产生最佳协同作用的病变，以揭示病理变化的性质。