Effects of Sympathetic Nerve Activity

描述(由申请人提供)： 对于视力丧失的老年退伍军人来说，精细运动技能的表现是具有挑战性的。眼-手的协调和感觉输入的整合是进行精细运动技能所必需的。衰老会导致感觉输入减少，并经常伴随着视力和运动控制能力的受损。对于视力丧失的老年退伍军人，缺乏有效的康复策略，需要制定出有效的康复策略，以增强神经系统在运动学习期间的适应能力(可塑性)。拟议项目的长期目标是帮助为失明的老年退伍军人开发创造性的康复干预和辅助技术。然而，在健康的年轻人学习精细运动技能的过程中，首先需要确定有效的干预措施，以增强神经可塑性。兴奋性N-甲基-D-天冬氨酸(NMDA)通路的激活可强烈增强运动皮质的神经可塑性，而抑制性γ-氨基丁酸(GABA)的激活则抑制其可塑性。虽然在药理学研究中已经提出了对NMD和GABA能功能的调节，但目前尚不清楚生理分泌的单胺是否通过增强交感神经活性来调节这些功能。我们最近发现，生理上增强的交感神经活动可以调节神经活动，从而更好地完成手部肌肉的精确任务。特别是，我们的初步观察表明，生理性增强的交感神经活动可以增强运动皮质内的易化(由NMDA介导)和减少运动皮质内的抑制(由GABA介导)。具体目的：研究在手部肌肉放松和执行精确任务时，交感神经生理活动增强对运动皮质皮质内抑制和促进的影响。假设：运动皮质内抑制被解除，皮质内促进功能增强，交感神经活动生理性增强，这是由于GABA能功能被抑制和NMDA能功能增强(我们的初步数据支持这一假设)。见第3-4节)。确定干预的生理预测因素可以帮助瞄准那些从干预中受益最大的个人。这可能导致基于交感神经系统和神经肌肉系统之间相互作用的新康复策略的发展。 公共卫生相关性： 亚特兰大退伍军人康复研发中心的使命是改善老年退伍军人的功能、独立性和生活质量。研究旨在了解损伤和残疾的潜在机制，并将其应用于创造性康复干预的设计、测试和评估。手的精细运动技能和视力随着年龄的增长而下降，这与老年人食指的运动输出变异性更大有关。为了开发有效的干预措施，有必要了解老年人运动输出变异性增加的基本神经生理机制。本研究的目的是试图了解交感神经活动增强是否影响健康年轻人的皮质兴奋性和运动输出变异性。我们还想了解，如果没有视觉反馈，这些影响是否会加剧。

DESCRIPTION (provided by applicant): Performance of fine motor skills is challenging for aging veterans with vision loss. Eye-hand coordination and integration of sensory input is essential to perform fine motor skills. Aging leads to reduced sensory input and is often accompanied by impaired vision and movement control. Efficient rehabilitation strategies for aging veterans with vision loss are lacking and need to be developed to enhance the adaptive capacity of the nervous system (plasticity) during motor learning. The long-term objectives of the proposed project are to help develop creative rehabilitative interventions and assistive technologies for aging veterans with vision loss. However, it is first necessary to identify effective interventions that would lead to enhancing neural plasticity during fine motor skill learning in healthy young adults. Neural plasticity in the motor cortex is strongly enhanced by the activation of excitatory N-methyl-D-aspartate (NMDA) pathways and inhibited by the activation of inhibitory gamma-aminobutyric acid (GABA). Although modulations of NMDAergic and GABAergic functions have been suggested in pharmacological studies, it is unknown whether physiologically secreted monoamines modulate these functions with heightened sympathetic nerve activity. We have recently found that physiologically heightened sympathetic nerve activity modulates neural activity for fine performance of precision tasks with a hand muscle. In particular, our preliminary observations suggested that physiologically heightened sympathetic nerve activity could enhance motor cortex intracortical facilitation (mediated by NMDA) and reduce motor cortex intracortical inhibition (mediated by GABA). Specific Aim: To examine the effects of physiologically heightened sympathetic nerve activity on motor cortex intracortical inhibition and facilitation when a hand muscle is relaxed and performing a precision task. Hypothesis: Motor cortex intracortical inhibition is disinhibited and intracortical facilitation is enhanced with physiologically heightened sympathetic nerve activity due to inhibited GABAergic functions and enhanced NMDAergic functions (The hypothesis is supported by our preliminary data. See Section 3-4). The identification of physiologic predictors for an intervention can help to target those individuals who best benefit from the intervention. This could lead to the development of new rehabilitative strategies based on the interactions between the sympathetic nervous system and the neuromuscular system PUBLIC HEALTH RELEVANCE: The mission of the Atlanta VA Rehabilitation R&D Center is to improve the function, independence, and quality of life of aging veterans. Research is directed towards understanding the mechanisms underlying impairments and disabilities, and applying this to the design, testing, and evaluation of creative rehabilitative interventions. The hand's fine motor skills and visual acuity are degraded with age, and this is related to greater motor output variability of the index finger in older adults. To develop effective interventions, it is imperative to understand the basic neuro-physiological mechanisms underlying this increased motor output variability in older adults.The objective of the proposed study is to try and understand whether heightened sympathetic nerve activity influences cortical excitability and motor output variability in healthy young adults. We also would like to understand if these effects are exacerbated with the absence of visual feedback.