This R21 proposal aims to employ a magnetic resonance spectroscopy (MRS) protocol to examine the relationship between the inhibitory neurotransmitter, ?-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.
This proposal will use a combination of magnetic resonance spectroscopy and transcranial magnetic stimulation as a novel approach to examine two inhibitory mechanisms important for response selection and initiation. The work builds on previous transcranial magnetic stimulation studies that have associated separate subregions of the frontal cortex with each of these mechanisms. Individual differences in the operation of these mechanisms will be explored by relating transcranial magnetic stimulation measures of motor system inhibition to local magnetic resonance spectroscopy measures of the inhibitory neurotransmitter gamma-aminobutyric acid, GABA.
