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.

Public Health Relevance

The proper function of the brain relies on a fine balance between neuronal excitation and inhibition. When inhibition mechanisms are compromised, uncontrolled brain activity can occur, thus leading to severe brain disorders such as for instance schizophrenia, epilepsy, or Parkinson's disease. Characterizing the neurochemical substrates that accompany inhibition in the working human brain is however an extremely challenging task, and has not been accomplished so far. With the present research, we will optimize non- invasive methodologies based on magnetic resonance spectroscopy that will allow measuring the dynamics of neurochemical concentrations during inhibition processes. The results of this research will be critical not only for our basic understanding of overall brain function, but also or the understanding and monitoring of many brain disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Small Research Grants (R03)
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Medical Imaging Study Section (MEDI)
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Babcock, Debra J
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University of Minnesota Twin Cities
Schools of Medicine
United States
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Bedna?ík, Petr; Tká?, Ivan; Giove, Federico et al. (2015) Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla. J Cereb Blood Flow Metab 35:601-10
Adanyeguh, Isaac M; Henry, Pierre-Gilles; Nguyen, Tra M et al. (2015) In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7. Mov Disord 30:662-70