Spinal cord contribution to motor skill learning

在过去的20年里，我实验室的心理物理学、多模式神经成像和临床人群研究增加了我们关于行为决定因素、神经网络和睡眠特征的知识基础，这些因素参与了运动技能行为的早期学习、巩固、自动化和长期保持。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，运动技能的学习是否只依赖于大脑的可塑性，或者这个记忆过程是否也取决于脊髓活动的变化。在NSERC的支持下，我们最近证明了脊髓在运动技能学习中确实发挥了作用。我们的结果显示，在年轻的健康受试者的C6-C8脊柱节段，新的运动序列(MSL)的学习产生了在前臂1诱发的Hoffman反射的显著减少，以及特定和局部的学习依赖的血氧水平依赖(BOLD)信号的增加。然而，尽管取得了这些进展，关于运动学习过程中的作用机制和脑-脊椎相互作用的几个基本问题仍然存在，因为这种变化也可能是脊椎上下行影响的结果。 在这次拨款续期中，我们打算在一系列独特的研究中填补这一空白，该系列研究旨在结合肌电(EMG)记录、磁刺激和电生理刺激，以及大脑和颈髓的同时任务相关和静息状态功能磁共振成像(FMRI)，研究运动学习中大脑和脊柱之间的相互作用。主要目标是： 1)确定我们在反映脊髓活动的H反射和BOLD信号中观察到的学习依赖性变化是否仅在MSL期间发现，或者是否推广到其他形式的习得过程、运动技能和学习阶段。 2)确定这种依赖学习的脊髓活动变化背后可能的神经生理学机制，以及这种变化如何与大脑活动相互作用。 更具体地说，为了解决第一个目标，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状态活动中观察到；b)研究脊髓在MSL早期和后期学习阶段中的作用；c)确定受试者在内隐学习新的动作序列时脊髓的活跃程度，而不是当他们被训练在一个明确的已知序列上时，该序列只会随着练习而变得更加内隐，以及d)探索脊髓是否也在我们适应感觉运动映射变化(另一种形式的运动技能，称为视觉运动适应)的能力中发挥作用。其次，为了解决第二个目标，我计划：a)评估MSL期间脊髓可塑性在多大程度上主要依赖于习惯性、突触前、突触后、脊髓固有或脊髓上机制或它们的组合，以及b)揭示导致脊髓水平运动学习依赖活动变化的行动机制(S)及其与脑活动的功能联系的神经元底物。上述实验将阐明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来获得和产生熟练的运动动作。从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