title: Comparing GABA-dependent physiological measures of inhibition with proton magnetic resonance spectroscopy measurement of GABA using ultra-high-field MRI.
abstract: Imbalances in glutamatergic (excitatory) and GABA (inhibitory) signalling within key brain networks are thought to underlie many brain and mental health disorders, and for this reason there is considerable interest in investigating how individual variability in localised concentrations of these molecules relate to brain disorders. Magnetic resonance spectroscopy (MRS) provides a reliable means of measuring, in vivo, concentrations of neurometabolites such as GABA, glutamate and glutamine that can be correlated with brain function and dysfunction. However, an issue of much debate is whether the GABA observed and measured using MRS represents the entire pool of GABA available for measurement (i.e., metabolic, intracellular, and extracellular) or is instead limited to only some portion of it. GABA function can also be investigated indirectly in humans through the use of non-invasive transcranial magnetic stimulation (TMS) techniques that can be used to measure cortical excitability and GABA-mediated physiological inhibition. To investigate this issue further we collected in a single session both types of measurement, i.e., TMS measures of cortical excitability and physiological inhibition and ultra-high-field (7 T) MRS measures of GABA, glutamate and glutamine, from the left sensorimotor cortex of the same group of right-handed individuals. We found that TMS and MRS measures were largely uncorrelated with one another, save for the plateau of the TMS IO curve that was negatively correlated with MRS-Glutamate (Glu) and intra-cortical facilitation (10ms ISI) that was positively associated with MRS-Glutamate concentration. These findings are consistent with the view that the GABA concentrations measured using the MRS largely represent pools of GABA that are linked to tonic rather than phasic inhibition and thus contribute to the inhibitory tone of a brain area rather than GABAergic synaptic transmission.
authors.affiliation: School of Psychology, University of Nottingham, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Dyke
authors.affiliation: School of Psychology, University of Nottingham, UK.
authors.forename: Sophia E
authors.initials: SE
authors.lastname: Pépés
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, UK.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Psychology, University of Nottingham, UK; Institute of Mental Health, School of Medicine, University of Nottingham, UK.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: School of Psychology, University of Nottingham, UK.
authors.forename: Hilmar P
authors.initials: HP
authors.lastname: Sigurdsson
authors.affiliation: School of Psychology, University of Nottingham, UK; Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Amelia
authors.initials: A
authors.lastname: Draper
authors.affiliation: Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Masud
authors.initials: M
authors.lastname: Husain
authors.affiliation: Institute of Cognitive Neuroscience, University College London, UK.
authors.forename: Parashkev
authors.initials: P
authors.lastname: Nachev
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, UK.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Gowland
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, UK.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Morris
authors.affiliation: School of Psychology, University of Nottingham, UK. Electronic address: Stephen.jackson@nottingham.ac.uk.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Jackson
mesh_terms: D000328:Adult; D019054:Evoked Potentials, Motor; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000502:physiology*; D009433:Neural Inhibition; D066244:Proton Magnetic Resonance Spectroscopy; D015203:Reproducibility of Results; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology
chemical_list: D005680:gamma-Aminobutyric Acid