Relationship of Prefrontal GABA to Inhibitory Mechanisms for Response Preparation

描述(由申请人提供)：这份R21提案旨在使用磁共振波谱(MRS)协议来检查额叶皮质中的抑制性神经递质伽马氨基丁酸(GABA)与运动系统动力学之间的关系，这是通过对运动皮质的经颅磁刺激(TMS)测量的。在PI的实验室中进行的TMS研究已经分离出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的反应之间的竞争，并与外侧前额叶皮质有关。另一种机制有助于防止冲动地执行选定的反应，并与背侧运动前皮质有关。然而，这两个抑制过程与其相关额叶皮质区域内GABA水平的关系尚未被研究。拟议的项目将调查这种关系 通过研究神经化学和神经生理学水平上的个体差异。该项目代表了PI的一个新的研究方向，具有很高的可行性。PI是马达系统和使用TMS作为工具来调查反应准备动态的专家。合作研究员理查德·马多克博士是使用MRS方法的专家，特别是在测量GABA方面。在马多克博士的指导下，以及最近在加州大学伯克利分校安装了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.