Relationship of Prefrontal GABA to Inhibitory Mechanisms for Response Preparation

描述（由申请人提供）：本R21提案旨在采用磁共振波谱（MRS）方案，以检查在运动选择和启动期间，额叶皮层中的抑制性神经递质γ-氨基丁酸（GABA）与运动系统动力学之间的关系，如运动皮层的经颅磁刺激（TMS）所测量的。在PI实验室进行的TMS研究分离了两种有助于选择和启动反应的抑制机制。一种机制有助于解决共同激活反应之间的竞争，与外侧前额叶皮层有关。另一种机制有助于防止冲动执行选定的反应，并与背侧前运动皮层有关。然而，这两个抑制过程的GABA水平在其相关的额叶皮层区域的关系还没有被调查。拟议的项目将调查这种关系 通过在神经化学和神经生理学水平上研究个体差异。该项目代表了PI的一个新的研究方向，但具有高度的可行性。PI是运动系统和使用TMS作为研究反应准备动力学的工具的专家。共同研究员Richard Maddock博士是使用MRS方法的专家，特别是用于测量GABA。在Maddock博士的指导下，以及最近在加州大学伯克利分校安装的MRS软件，这项工作的基础设施已经到位。

DESCRIPTION (provided by applicant): This R21 proposal aims to employ a magnetic resonance spectroscopy (MRS) protocol to examine the relationship between the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), in the frontal cortex and motor system dynamics during the selection and initiation of movements as measured with transcranial magnetic stimulation (TMS) of the motor cortex. TMS studies conducted in the PI's laboratory have dissociated two inhibitory mechanisms that contribute to the selection and initiation of responses. One mechanism helps to resolve competition among co-activated responses and is associated with lateral prefrontal cortex. The other mechanism helps prevent impulsive execution of a selected response and is associated with dorsal premotor cortex. However, the relationship of these two inhibitory processes to levels of GABA within their associated frontal cortical regions has not been investigated. The proposed project will investigate this relationship through the study of individual differences at the neurochemical and neurophysiological level. The project represents a new research direction for the PI, yet is highly feasible. The PI is an expert on the motor system and the use of TMS as a tool for investigating the dynamics of response preparation. The co-investigator Dr. Richard Maddock is an expert in the use of MRS methods, specifically for measuring GABA. With Dr. Maddock's guidance, and the recent installation of MRS software at UC Berkeley, the infrastructure is in place for this work.