Behavioral and Neurophysiological Mechanisms of Interference in Skill Learning

描述(由申请人提供)： 这个项目的目的是为了更好地了解干扰技能学习的神经生理学基础。连续练习运动任务会干扰学习，然而，如果在两项技能的训练之间有足够的时间(即6小时)，则干扰较弱。尽管对干扰的行为后果进行了广泛的研究，但其背后的神经生理学机制在很大程度上是未知的。这一点非常重要，因为与运动学习相关的皮质可塑性变化可能代表了阻止第二项任务学习的神经生理机制。例如，动物研究表明，运动学习诱导的初级运动皮质中长时程增强(LTP)的变化也与维持更多LTP的能力降低有关，这种现象被称为LTP饱和或稳态可塑性。在人类身上也观察到了动态平衡可塑性。这项建议的总体目的是测试技能学习后的动态平衡可塑性是否是行为干预的机制之一。这将通过使用无创经颅直流电刺激(TDC)在连续视觉等长收缩任务(SVIPT)的训练后诱导LTP样可塑性变化来实现，无论是在学习、无学习的情况下执行还是在有干扰的学习的背景下。为了确定训练和tDC引起的运动皮质兴奋性的变化，将使用经颅磁刺激(TMS)来评估与在这些背景下练习任务相关的饱和程度(内稳态可塑性)。在目标1中，我假设掌握一项技能将导致阳极tDCs(稳态塑性现象)的LTP样塑性效应饱和，并且学习一项技能后这种稳态塑性的大小将与保持和干扰的大小成正比。此外，我还将评估时间对神经生理学干扰的影响。在目标2中，我假设在两种技能训练之间的6小时将与阳极tDCs(缺乏饱和)的LTP样可塑性的恢复有关，并且这种恢复将与干扰的减少相关。这些结果将表明，学习导致的初级运动皮质的LTP样变化至少是行为干扰的神经底物之一。如果这是真的，体内平衡可塑性现象可以成为干扰的预测指标。重要的是，提高我们对技能学习和干预的基本机制的理解有明显的临床好处。这些发现可能会影响个人如何训练运动技能，或许更重要的是，如何在中风等脑损伤后的患者中进行康复训练。此外，这项研究可能会被证明是有用的，以开发干预措施，以加强对多任务的学习。 公共卫生相关性： 这项研究将加深我们对技能学习的一些基本机制的理解。这些发现可能会影响个人如何训练运动技能，或许更重要的是，如何为脑功能障碍患者提供康复训练练习。此外，这项工作还可能导致针对这些机制的干预，作为加强运动学习和康复的一种手段。

DESCRIPTION (provided by applicant): The goal of this project is to gain a better understanding of the neurophysiological substrates underlying interference of skill learning. Practicing motor tasks in close succession can interfere with learning, however, if sufficient time passes between the training of 2 skills (i.e. 6hrs), then interference is weaker. Despite extensive study about the behavioral consequences of interference, the neurophysiologic mechanisms underlying it are largely unknown. This is very important because the cortical plasticity changes associated with motor learning may represent the neurophysiological mechanisms that prevent learning of a second task. For instance, animal studies have shown motor learning induced long-term potentiation (LTP) changes in the trained primary motor cortex are also associated with a reduced capacity to sustain more LTP, a phenomenon known as LTP-saturation or homeostatic plasticity. Homeostatic plasticity has also been observed in humans. The overall purpose of this proposal is to test whether homeostatic plasticity following skill learning is one of the mechanisms underlying behavioral interference. This will be accomplished by using non-invasive transcranial direct current stimulation (tDCS) to induce LTP-like plasticity changes after training of a sequential visual isometric pinch task (SVIPT) either in the context of learning, performance with no learning, or learning with interference. To determine excitability changes in the motor cortex resulting from training and tDCS, transcranial magnetic stimulation (TMS) will be used to assess the magnitude of saturation (homeostatic plasticity) associated with practicing the task in these contexts. In Aim 1, I hypothesize that the acquisition of a skill will result in the saturation of the LTP-like plasticity effects of anodal tDCS (homeostatic plasticity phenomena), and that the magnitude of this homeostatic plasticity after learning a skill will be proportional to the magnitude of retention and interference. In addition, I will assess the effect of time on the neurophysiology of interference. In Aim 2, I hypothesize that 6 hours of time between training of 2 skills will be associated with a restoration of the LTP-like plasticity of anodal tDCS (lack of saturation), and that this restoration will be associated with a decrease in interference. These results would indicate that LTP-like changes in the primary motor cortex resulting from learning are at least one of the neural substrates underlying behavioral interference. If this holds true the homeostatic plasticity phenomena can become a predictor of interference. Importantly, improving our understanding of the basic mechanisms underlying skill learning and interference has clear clinical benefits. These findings have the potential to impact how individuals train motor skills, and perhaps more importantly, how rehabilitation training exercises are delivered in patients after brain lesions like stroke. Furthermore, this research may prove useful to develop interventions to enhance learning of multiple tasks. PUBLIC HEALTH RELEVANCE: This research will improve our understanding of some of the basic mechanisms underlying skill learning. These findings have the potential to impact how individuals train motor skills, and perhaps more importantly, how rehabilitation training exercises are delivered in patients with brain dysfunction. Furthermore, this work could also lead to interventions targeting these mechanisms as a means to augment motor learning and rehabilitation.