Functional MRS at 7T to Study Neuronal Inhibition in Humans

DESCRIPTION (provided by applicant): The characterization of the underlying metabolic/neurochemical events of neuronal firing suppression in the working human brain is a challenging task. Proton magnetic resonance spectroscopy (MRS) allows the non- invasive measurement of metabolite concentrations in the human brain. However, the low sensitivity of proton MRS can limit the reliability and accuracy of the method to detect small variations in the concentration of metabolites, especially of those present in low concentration, such as glucose, lactate or g-aminobutyric acid (GABA). These limitations impair a robust investigation of neuronal processes which produce subtle changes in the neurochemical profile of the brain, such as neuronal firing suppression. In this project we will benefit from the increased sensitivity offered by 7T scanners to enable the reliable and accurate detection of changes in the brain neurochemical profile which are critical to characterize neuronal firing suppression. By conducting studies of functional MRS at 7T, we have in the past obtained robust results of multiple metabolite changes during functional paradigms of increased neuronal activity in the primary visual cortex. These results were proven to be extremely helpful to understand brain metabolism in physiological conditions. With the present project, we will extend this technology to further address the metabolic / neurochemical substrates of neuronal inhibition. The opportunity to measure inhibitory (GABA) and excitatory (glutamate) neurotransmitters, as well as the fuels of the brain (mainly glucose and lactate), is critical to gain comprehensive insight into the metabolic/neurochemical correlates of inhibition. This research will provide new experimental evidence to help understand neuronal inhibition in the human brain, which is important not only for our basic understanding of overall brain function, but also for the understanding and monitoring of many brain disorders such as schizophrenia, epilepsy or Parkinson's disease.