The inhibitory neurotransmitter GABA has a central role in control and tuning of excitatory neuronal activity. GABA can be detected non-invasively using 1H magnetic resonance spectroscopy (MRS). We have recently shown that individuals with more GABA in occipital cortex tend to give smaller responses to visual stimuli as measured by functional magnetic resonance imaging (fMRI), suggesting that individual differences between healthy subjects may be a useful tool to investigate the mechanisms underlying the fMRI response. Understanding the relationship between the metabolic demands of excitatory and inhibitory neuronal activity and the activation recorded by fMRI is an important task in neuroscience. The overall goal of this R21 application is to investigate whether GABA concentration correlates with fMRI activation amplitude across the whole brain. This will be addressed by progressing from task activation fMRI to resting-state fMRI and from multiple single-voxel MRS measurements to spectroscopic imaging (MRSI) of GABA.

Public Health Relevance

Functional magnetic resonance imaging (fMRI) is a very powerful method that is used by scientists to see which areas of the brain are used to perform different tasks, and to look for functional differences between the brains of healthy subjects and patients. GABA is a neurotransmitter, a chemical that is used for signaling in the brain, which is used by inhibitory neurons. This project will investigate how the size of fMRI signals is related to the concentration of GABA in different regions of the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS077300-01A1
Application #
8383863
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Babcock, Debra J
Project Start
2012-08-20
Project End
2014-07-31
Budget Start
2012-08-20
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$217,790
Indirect Cost
$60,399
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Mikkelsen, Mark; Loo, Rachelle S; Puts, Nicolaas A J et al. (2018) Designing GABA-edited magnetic resonance spectroscopy studies: Considerations of scan duration, signal-to-noise ratio and sample size. J Neurosci Methods 303:86-94
Edden, Richard A E; Oeltzschner, Georg; Harris, Ashley D et al. (2016) Prospective frequency correction for macromolecule-suppressed GABA editing at 3T. J Magn Reson Imaging 44:1474-1482
Harris, Ashley D; Puts, Nicolaas A J; Edden, Richard A E (2015) Tissue correction for GABA-edited MRS: Considerations of voxel composition, tissue segmentation, and tissue relaxations. J Magn Reson Imaging 42:1431-40
Harris, Ashley D; Puts, Nicolaas A J; Anderson, Brian A et al. (2015) Multi-regional investigation of the relationship between functional MRI blood oxygenation level dependent (BOLD) activation and GABA concentration. PLoS One 10:e0117531
Haag, Lauren M; Heba, Stefanie; Lenz, Melanie et al. (2015) Resting BOLD fluctuations in the primary somatosensory cortex correlate with tactile acuity. Cortex 64:20-8
Harris, Ashley D; Puts, Nicolaas A J; Barker, Peter B et al. (2015) Spectral-editing measurements of GABA in the human brain with and without macromolecule suppression. Magn Reson Med 74:1523-9
Mullins, Paul G; McGonigle, David J; O'Gorman, Ruth L et al. (2014) Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. Neuroimage 86:43-52
Harris, Ashley D; Glaubitz, Benjamin; Near, Jamie et al. (2014) Impact of frequency drift on gamma-aminobutyric acid-edited MR spectroscopy. Magn Reson Med 72:941-8
Edden, Richard A E; Puts, Nicolaas A J; Harris, Ashley D et al. (2014) Gannet: A batch-processing tool for the quantitative analysis of gamma-aminobutyric acid–edited MR spectroscopy spectra. J Magn Reson Imaging 40:1445-52
Puts, Nicolaas A J; Barker, Peter B; Edden, Richard A E (2013) Measuring the longitudinal relaxation time of GABA in vivo at 3 Tesla. J Magn Reson Imaging 37:999-1003

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