Motor Skill and the Cortical Motor Areas

项目摘要 获得和保持熟练的顺序动作是人类行为的基本组成部分。 我们仍然对皮质运动区发生可塑性变化的位置和时间知之甚少， 保持熟练的连续动作。在这里，我们建议研究学习的时间演变， 维持初级运动皮层（M1）和背侧运动前皮层（PMd）的熟练顺序运动 通过对这些区域的信息存储进行随机操纵。 我们将训练猴子完成两项任务。在一项任务中，猴子执行连续的到达 由记忆引导的动作记忆引导顺序动作任务的技能是通过以下方式获得的： 相当的实践。在控制任务中，猴子在视觉线索的引导下进行伸手动作。 我们的初步数据表明，注射蛋白质合成抑制剂或DNA抑制剂， 甲基化到猴子的M1破坏了获得的顺序运动的表现，而不影响 视觉引导下的伸手动作我们将应用这些方法来研究自然和时间 M1和PMd的可塑性过程，支持广泛的学习和维护， 练习运动技能。首先，确定连续运动的神经轨迹是否是逐渐的 在M1中通过扩展实践巩固，我们将在M1中注入蛋白质合成抑制剂， 在学习顺序运动的时间点。我们假设运动技能是重复的 每次受试者练习时，通过蛋白质合成巩固，并且巩固率下降 随着学习的进行。第二，为了确定PMd何时参与学习 运动元件的顺序，我们将注射蛋白质合成的抑制剂，在多个时间到PMd 在学习连续动作的过程中。我们假设M1和PMd的学习过程 在不同的时间框架内运行。第三，确定M1和PMd是否成为长期储存场所 对于所获得的连续运动，并且对于维持所获得的连续运动仍然至关重要。 运动时，我们将向这些区域注射DNA甲基化抑制剂。我们假设注射会 在长期练习后，破坏记忆引导的顺序运动的维持， 猴子需要重新学习序列以恢复注射后的表现。 完成拟议的研究将扩大我们的时间演变的理解， 学习，因为动物慢慢地成为高度熟练的持续长期的实践和巩固。这一水平 运动序列的专门知识从来没有在啮齿动物中研究过，也很少在猴子中研究，但这是一个共同的特征， 人类日常运动表现。研究结果将为制定新的战略提供信息， 获得运动技能和增强中风或创伤性脑损伤后的功能恢复。

PROJECT SUMMARY The acquisition and retention of skilled sequential movements is a fundamental part of human behavior. We still know little about where and when plastic changes occur in the cortical motor areas to learn and maintain skilled sequential movements. Here, we propose to study the temporal evolution of the learning and maintenance of skilled sequential movements in primary motor cortex (M1) and dorsal premotor cortex (PMd) by pharmacologically manipulating information storage in these areas. We will train monkeys to perform two tasks. In one task, the monkeys perform sequential reaching movements guided by memory. Skill on the memory-guided sequential movements task is acquired through considerable practice. For a control task, the monkeys perform reaching movements guided by visual cues. Our preliminary data showed that an injection of an inhibitor for protein synthesis or an inhibitor for DNA methylation into M1 of monkeys disrupted the performance of acquired sequential movements without affecting the performance of visually guided reaching. We will apply these approaches to examine the nature and time course of plasticity processes in M1 and PMd that support the learning and maintenance of extensively practiced motor skills. First, to determine whether the neural trace for sequential movements is gradually consolidated in M1 with extended practice, we will inject an inhibitor of protein synthesis into M1 at multiple time points during learning of sequential movements. We hypothesize that the motor skill is repetitively consolidated through protein synthesis every time a subject practice, and that the rate of consolidation declines as learning proceeds. Second, to determine when PMd is involved in learning the associations between movement elements in a sequence, we will inject an inhibitor of protein synthesis into PMd at multiple time points during learning of sequential movements. We hypothesize that learning processes in M1 and PMd operate in different time frames. Third, to determine whether M1 and PMd become sites of long-term storage for the acquired sequential movements and remain critical for the maintenance of the acquired sequential movements, we will inject an inhibitor of DNA methylation into these areas. We postulate that the injection will disrupt the maintenance of memory-guided sequential movements after long term practice and that the monkey will need to relearn the sequence to recover his performance after the injection. Completion of the proposed studies will expand our understanding of the temporal evolution of the learning, as animals slowly become highly skilled with ongoing long-term practice and consolidation. That level of motor sequence expertise is never studied in rodents and rarely in monkeys, yet it is a common feature of everyday human motor performance. The results will provide information to develop new strategies for acquiring motor skills and enhance functional recovery following stroke or traumatic brain injury.