Cerebral Mechanisms of Skill Learning in Humans

描述(由申请人提供)： 这个项目的目标是了解前额叶和运动基底节-丘脑皮质环如何有助于人类的运动技能学习。该项目专门针对一种运动技能学习形式，即随着时间的推移，通过练习将移动速度和准确性调整为视觉输入，就像学习使用计算机鼠标一样。这些研究将评估前额-基底节环路发出需要改变运动的信号，以及皮质-基底节运动回路较晚起作用以实现所需的运动适应的假设。基底节被认为是合成来自两个环的皮质信息的地方，苍白球内侧部和丘脑底核启动了速度变化。FMRl方法将用于比较正常人和运动障碍患者(帕金森氏症和肌张力障碍患者)在运动技能学习过程中激活的大脑区域，这些患者的学习可能会受到影响。接下来，在这些相同的运动行为过程中，将在前额叶皮质或背外侧前额叶皮质、苍白球和丘脑底核以及丘脑同时进行多个单细胞记录，以确定与信号相关的神经变化，并在两个脑环中设置相关变化。在人类前脑进行行为神经生理学实验的独特机会现在可能发生在运动障碍的受试者身上，他们接受神经生理标测来指导大脑深部刺激器的放置。可以直接评估大脑皮质和深层结构在学习中的作用，因为受试者可以在记录过程中进行视觉引导的手臂运动。这个项目将有助于提供有关额叶皮质和基底神经节回路在运动技能获得过程中相互作用的重要信息。因为我们正在将帕金森氏病和肌张力障碍的受试者与对照受试者进行比较，所以将获得有关导致这些运动障碍的皮质和皮质下过程的重要新信息。

DESCRIPTION (provided by applicant): The goal of this project is to understand how the prefrontal- and motor-basal ganglia-thalamocortical loops contribute to motor skill learning in humans. The project specifically addresses a form of motor skill learning where movement speed and accuracy is scaled to visual input over time with practice, as in learning to use a computer mouse. The studies will evaluate the hypothesis that the prefrontal-basal ganglia loop signals the need to change movement and that cortical-basal ganglia motor circuit acts later to implement the movement adaptation required. The basal ganglia is hypothesized to be the site where the cortical information from the two loops is synthesized, with the globus pallidus pars interna and the subthalamic nucleus initiating the velocity changes. FMRl methods will be used to compare cerebral regions activated during motor skill learning in normal humans and movement disorders patients (parkinson's and dystonia), where learning may be compromised. Next, simultaneous, multiple single cell recordings will be made in either the premotor or dorsolateral prefrontal cortex, globus pallidus and subthalamic nucleus, and thalamus during these same motor behaviors to identify neural changes associated with signal and set related changes in the two cerebral loops. A unique opportunity to carry out behavioral neurophysiology experiments in human forebrain is now possible in movement-disordered subjects, who undergo neurophysiological mapping to guide placement of a deep brain stimulator. Direct evaluation of the role of cortical and deep cerebral structures in learning can be carried out because subjects can perform visually guided arm movements during recording. This project will help provide important information about the ways in which the frontal cortical and basal ganglia circuits interact during motor skill acquisition. Because we are comparing subjects with Parkinson's disease and dystonia to control subjects, important new information about the cortical and subcortical processes contributing to these motor disorders will be obtained.