Spinal cord contribution to motor skill learning

在过去的20年里，心理物理学，多模态神经成像和临床人群研究在我的实验室增加了我们的知识基础的行为决定因素，神经网络和睡眠特征介导的早期学习，巩固，自动化和长期保留的运动技能行为。例如，我的工作使我能够更好地理解皮质-纹状体和皮质-小脑系统在运动学习中的特殊贡献。然而，一个被神经科学界完全忽视的重要问题是，运动技能学习是否仅依赖于大脑的可塑性，或者这种记忆过程是否也依赖于脊髓活动的变化。在NSERC的支持下，我们最近证明了脊髓确实在运动技能学习中发挥作用。我们的研究结果表明，一个新的运动序列（MSL）的学习产生了显着减少的霍夫曼反射引起的前臂1，以及一个特定的和本地化的学习依赖性增加血氧水平依赖（BOLD）的信号在C6-C8脊髓节段的年轻健康受试者。然而，尽管取得了这些进展，一些基本的问题仍然存在关于运动学习过程中的作用机制和脑-脊柱相互作用，因为这些变化也可能是由于脊髓上的影响。 在这次资助更新中，我们打算在一系列独特的研究中填补这一空白，这些研究旨在研究运动学习中的脑-脊柱相互作用，这些研究结合了肌电图（EMG）记录、磁和电生理刺激以及大脑和颈脊髓的同步任务相关和静息状态功能磁共振成像（fMRI）。主要目标是： 第一章 确定我们在H反射和BOLD信号中观察到的反映脊髓活动的学习依赖性变化是否仅在MSL期间发现，或者它是否推广到其他形式的获取过程，运动技能和学习阶段。 （二） 确定这种学习依赖性脊髓活动变化背后可能的神经生理机制，以及这种机制如何与大脑活动相互作用。 更具体地说，为了实现第一个目标，我建议：a）测试在MSL期间获得的运动记忆痕迹是否也可以在脊髓静息态活动中观察到，B）研究脊髓在MSL的早期和晚期学习阶段中的作用，c）、为了确定当受试者内隐地学习新的运动序列时与当他们在一个明确已知的序列上训练，只有通过练习才变得更加隐含，d）探索脊髓是否也在我们适应感觉运动映射变化的能力中发挥作用（另一种形式的运动技能称为：视觉适应）。其次，为了实现第二个目标，我计划：a）评估MSL期间脊髓可塑性主要依赖于习惯化、突触前、突触后、脊髓本体或脊髓上机制或其组合的程度，和B）揭示负责脊髓水平的运动学习依赖性活动变化的作用机制的神经元基质，及其与大脑活动的功能联系。上述实验将揭示脊髓在运动学习过程中是否表现出局部可塑性，这种现象发生的条件和机制是什么，以及脊髓和大脑如何协同工作以获得和产生熟练的运动动作。在这些研究中获得的见解将导致基于运动学习的各种康复技术的开发和评估

For the last 20 years, psychophysical, multimodal neuroimaging and clinical population studies in my laboratory have increased our knowledge base of the behavioural determinants, neural networks and sleep characteristics mediating the early learning, consolidation, automatization and long-term retention of motor skilled behaviors. My work has allowed to better understand the specialized contribution from the cortico-striatal and cortico-cerebellar systems in motor learning, for example. Yet one important issue that has entirely been overlooked by the neuroscientific community is whether motor skill learning relies on brain plasticity only, or whether this memory process depends on spinal cord activity changes as well. With support from NSERC, we have recently demonstrated that the spinal cord does play a role in motor skill learning. Our results reveal that the learning of a new sequence of movements (MSL) produces a significant reduction of the Hoffman reflex elicited in the forearm1, as well as a specific and localized learning-dependent increase in blood oxygenated level dependent (BOLD) signal in C6-C8 spinal segments of young healthy subjects. Yet despite such advances, several fundamental questions remain regarding the mechanisms of action and brain-spine interaction during motor learning as such changes might also result from descending supraspinal influences. In this grant renewal, we intend to fill out this gap in a unique series of studies aimed at investigating brain-spine interactions in motor learning using a combination of electromyographic (EMG) recordings, magnetic and electrophysiological stimulation, as well as simultaneous tasks-related and resting-state functional magnetic resonance imaging (fMRI) of the brain and cervical spinal cord. The main objectives are: 1) To determine whether the learning-dependent changes that we observed in H-reflex and BOLD signal reflecting spinal cord activity are only found during MSL, or whether it generalizes to other forms of acquisition processes, motor skills and learning stages. 2) To identify the possible neurophysiological mechanisms underlying this learning-dependent spinal change in activity, and how this interacts with brain activity. More specifically, to address the first objective, I propose: a) to test whether the motor memory trace acquired during MSL can also be observed in spinal resting-state activity, b) to study the role of the spinal cord in both early and late learning phases of MSL, c) to determine the extent to which the spinal cord is active when subjects are implicitly learning a new sequence of movements as compared to when they are trained on an explicitly known sequence that only becomes more implicit with practice, and d) to explore whether the spinal cord also plays a role in our ability to adapt to changes in sensorimotor mapping (another form of motor skill called: visuomotor adaptation). Second, to address the second objective, I then plan: a) to assess the extent to which spinal plasticity during MSL relies mostly on habituation, presynaptic, postsynaptic, propriospinal or supraspinal mechanisms or a combination thereof, and b) to uncover the neuronal substrate underlying the mechanism(s) of action responsible for the change in motor learning-dependent activity at the spinal level, and its (their) functional link with brain activity. The experiments above will shed light on whether the spinal cord shows local plasticity during motor learning, what are the conditions and mechanisms under which such phenomena occurs, and how the spinal cord and brain work in concert to acquire and produce skilled motor actions. Insights gained in these studies will then lead to development and assessment of various rehabilitation techniques based on motor learning