Effects of Sympathetic Nerve Activity

描述（由申请人提供）： 精细运动技能的表现是具有挑战性的老年退伍军人视力丧失。眼手协调和感觉输入的整合对于执行精细运动技能至关重要。衰老导致感觉输入减少，并且通常伴有视力和运动控制受损。缺乏有效的康复策略，为老年退伍军人视力丧失，需要开发，以提高适应能力的神经系统（可塑性）在运动学习。该拟议项目的长期目标是帮助患有视力丧失的老年退伍军人开发创造性的康复干预措施和辅助技术。然而，首先需要确定有效的干预措施，这将导致在健康的年轻人精细运动技能学习过程中增强神经可塑性。运动皮层中的神经可塑性通过兴奋性N-甲基-D-天冬氨酸（NMDA）通路的激活而强烈增强，并通过抑制性γ-氨基丁酸（GABA）的激活而抑制。虽然在药理学研究中已经提出了NMDA能和GABA能功能的调节，但尚不清楚生理分泌的单胺是否通过增强的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调节神经活动，以便用手部肌肉执行精确任务。特别是，我们的初步观察表明，生理上提高交感神经活动可以增强运动皮层皮层内的促进（由NMDA介导）和减少运动皮层内抑制（由GABA介导）。具体目标：研究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层内抑制和易化的影响。假设：由于GABA能功能抑制和NMDA能功能增强，运动皮质皮质内抑制被解除，皮质内易化随着交感神经活动的生理增强而增强（该假设得到我们初步数据的支持）。参见第3-4节）。确定干预的生理预测因子有助于确定最佳受益于干预的个体。这可能导致基于交感神经系统和神经肌肉系统之间的相互作用的新的康复策略的发展 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机制，并将其应用于创造性康复干预措施的设计，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。为了制定有效的干预措施，有必要了解基本的神经生理机制，这种增加运动输出的变异性在老年adultes. Objective提出的研究是尝试和了解交感神经活动是否会影响皮质兴奋性和运动输出的变异性在健康的年轻人。我们还想知道，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.