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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

基本信息

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
项目类别：
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

项目摘要

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，这会导致行动不便