Activation induced changes in GABA: Functional MRS at 7T with MEGA-sLASER

&NA; Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non‐invasively. However, only limited information on the dynamic functional response of &ggr;‐aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation‐induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies. The Mescher‐Garwood‐semi‐localised by adiabatic selective refocusing (MEGA‐sLASER) sequence was developed at 7 T to obtain the time course of GABA concentration without macromolecular contamination. A significant decrease (−12±5%) in the GABA to total creatine ratio (GABA/tCr) was observed in the motor cortex during a period of 10 min of hand‐clenching, compared to an initial baseline level (GABA/tCr =0.11±0.02) at rest. An increase in the Glx (glutamate and glutamine) to tCr ratio was also found, which is in agreement with previous findings. In contrast, no significant changes in NAA/tCr and tCr were detected. With consistent and highly efficient editing performance for GABA detection and the advantage of visually identifying GABA resonances in the spectra, MEGA‐sLASER is demonstrated to be an effective method for studying of dynamic changes in GABA at 7 T.

[1]  Rolf Gruetter,et al.  Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla , 2014, NeuroImage.

[2]  A. J. Kresge,et al.  Proton NMR Chemical Shifts of Hydronium and Hydroxyl Ions , 1963 .

[3]  P. Bottomley.  Spatial Localization in NMR Spectroscopy in Vivo , 1987, Annals of the New York Academy of Sciences.

[4]  Charlotte J. Stagg,et al.  Magnetic Resonance Spectroscopy as a tool to study the role of GABA in motor-cortical plasticity , 2014, NeuroImage.

[5]  René S. Kahn,et al.  GABA and glutamate in schizophrenia: A 7 T 1H-MRS study , 2014, NeuroImage: Clinical.

[6]  K. Uğurbil,et al.  Sensitivity of single-voxel 1H-MRS in investigating the metabolism of the activated human visual cortex at 7 T. , 2006, Magnetic resonance imaging.

[7]  Vanhamme,et al.  Improved method for accurate and efficient quantification of MRS data with use of prior knowledge , 1997, Journal of magnetic resonance.

[8]  Rolf Gruetter,et al.  Direct in vivo measurement of human cerebral GABA concentration using MEGA‐editing at 7 Tesla , 2002, Magnetic resonance in medicine.

[9]  L. Xin,et al.  Investigating the Metabolic Changes due to Visual Stimulation using Functional Proton Magnetic Resonance Spectroscopy at 7 T , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  Mark J Lowe,et al.  In vivo magnetic resonance spectroscopy measurement of gray-matter and white-matter gamma-aminobutyric acid concentration in sensorimotor cortex using a motion-controlled MEGA point-resolved spectroscopy sequence. , 2011, Magnetic resonance imaging.

[11]  C. Rae,et al.  Activity‐dependent γ‐aminobutyric acid release controls brain cortical tissue slice metabolism , 2011, Journal of neuroscience research.

[12]  E. Martin,et al.  In vivo detection of GABA and glutamate with MEGA‐PRESS: Reproducibility and gender effects , 2011, Journal of magnetic resonance imaging : JMRI.

[13]  Peter B Barker,et al.  Spatial effects in the detection of γ‐aminobutyric acid: Improved sensitivity at high fields using inner volume saturation , 2007, Magnetic resonance in medicine.

[14]  Shi-Jiang Li,et al.  Differentiation of metabolic concentrations between gray matter and white matter of human brain by in vivo 1H magnetic resonance spectroscopy , 1998, Magnetic resonance in medicine.

[15]  R. Mattson,et al.  Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[16]  John C Gore,et al.  A practical guide to robust detection of GABA in human brain by J-difference spectroscopy at 3 T using a standard volume coil. , 2007, Magnetic resonance imaging.

[17]  Silvia Mangia,et al.  Functional MRS at 7T and long TE , 2016 .

[18]  Charlotte J. Stagg,et al.  Magnetic Resonance Spectroscopy: Tools for Neuroscience Research and Emerging Clinical Applications , 2013 .

[19]  R. Edden,et al.  Gannet: A batch‐processing tool for the quantitative analysis of gamma‐aminobutyric acid–edited MR spectroscopy spectra , 2014, Journal of magnetic resonance imaging : JMRI.

[20]  Rex E. Jung,et al.  A novel technique to study the brain's response to pain: Proton magnetic resonance spectroscopy , 2005, NeuroImage.

[21]  N. Logothetis,et al.  Dynamics of lactate concentration and blood oxygen level‐dependent effect in the human visual cortex during repeated identical stimuli , 2007, Journal of neuroscience research.

[22]  Jullie W Pan,et al.  Measurements of human cerebral GABA at 4.1 T using numerically optimized editing pulses , 1998, Magnetic resonance in medicine.

[23]  Peter R Luijten,et al.  Efficient spectral editing at 7 T: GABA detection with MEGA‐sLASER , 2012, Magnetic resonance in medicine.

[24]  R. Edden,et al.  In vivo magnetic resonance spectroscopy of GABA: a methodological review. , 2012, Progress in nuclear magnetic resonance spectroscopy.

[25]  Darren Price,et al.  Methodology for improved detection of low concentration metabolites in MRS: Optimised combination of signals from multi-element coil arrays , 2014, NeuroImage.

[26]  Rolf Gruetter,et al.  Fast, noniterative shimming of spatially localized signals. In vivo analysis of the magnetic field along axes , 1992 .

[27]  Gareth J Barker,et al.  Concentrations and magnetization transfer ratios of metabolites in gray and white matter , 2006, Magnetic resonance in medicine.

[28]  Jason A. Koutcher,et al.  J‐difference lactate editing at 3.0 Tesla in the presence of strong lipids , 2008, Journal of magnetic resonance imaging : JMRI.

[29]  J C Rothwell,et al.  Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex , 2011, The Journal of physiology.

[30]  Peter Jezzard,et al.  Efficient γ‐aminobutyric acid editing at 3T without macromolecule contamination: MEGA‐SPECIAL , 2011, NMR in biomedicine.

[31]  H. Johansen-Berg,et al.  The Role of GABA in Human Motor Learning , 2011, Current Biology.

[32]  K Ugurbil,et al.  In vivo 1H NMR spectroscopy of the human brain at 7 T , 2001, Magnetic resonance in medicine.

[33]  K. Uğurbil,et al.  Sustained Neuronal Activation Raises Oxidative Metabolism to a New Steady-State Level: Evidence from 1H NMR Spectroscopy in the Human Visual Cortex , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  Jonathan W. Peirce,et al.  PsychoPy—Psychophysics software in Python , 2007, Journal of Neuroscience Methods.

[35]  H. Möhler,et al.  GABAA receptor diversity and pharmacology , 2006, Cell and Tissue Research.

[36]  C. Rae.  A Guide to the Metabolic Pathways and Function of Metabolites Observed in Human Brain 1H Magnetic Resonance Spectra , 2013, Neurochemical Research.

[37]  Mauro DiNuzzo,et al.  Neurochemical and BOLD Responses during Neuronal Activation Measured in the Human Visual Cortex at 7 Tesla , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[38]  Theodoros N. Arvanitis,et al.  A constrained least‐squares approach to the automated quantitation of in vivo 1H magnetic resonance spectroscopy data , 2011, Magnetic resonance in medicine.

[39]  P. Allen,et al.  In vivo NMR spectroscopy. , 1990, Basic life sciences.

[40]  R. Gruetter,et al.  In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time , 1999, Magnetic resonance in medicine.

[41]  Peter G. Morris,et al.  Increased GABA Contributes to Enhanced Control over Motor Excitability in Tourette Syndrome , 2014, Current Biology.

[42]  Ron Kupers,et al.  Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex in man , 2009, Pain.

[43]  Jürgen R. Reichenbach,et al.  In vivo detection of acute pain-induced changes of GABA+ and Glx in the human brain by using functional 1H MEGA-PRESS MR spectroscopy , 2015, NeuroImage.

[44]  M. Garwood,et al.  Simultaneous in vivo spectral editing and water suppression , 1998, NMR in biomedicine.

[45]  D. Klomp,et al.  In vivo GABA T2 determination with J‐refocused echo time extension at 7 T , 2013, NMR in biomedicine.

[46]  Semiha Aydin,et al.  Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE 1H MRS at 7 T , 2017, NMR in biomedicine.

[47]  Mark Hallett,et al.  Impaired brain GABA in focal dystonia , 2002, Annals of neurology.

[48]  V. Govindaraju,et al.  Proton NMR chemical shifts and coupling constants for brain metabolites , 2000, NMR in biomedicine.

[49]  Leonie Lampe,et al.  Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome , 2016, Brain : a journal of neurology.

[50]  C. John Evans,et al.  Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA , 2014, NeuroImage.

[51]  Rolf Gruetter,et al.  MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T , 2009, Magnetic resonance in medicine.

[52]  Mark Tommerdahl,et al.  Title: Reduced Gabaergic Inhibition and Abnormal Sensory Symptoms in Children with Tourette Syndrome Running Head: Abnormal Gaba Levels and Sensory Processing in Ts Submitted for the Steven Hsiao Special Issue Nicolaas Puts, Phd Author Contributions Introduction , 2022 .

[53]  Peter G. Morris,et al.  tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: A 7 T magnetic resonance spectroscopy study , 2014, NeuroImage.

[54]  Richard A. E. Edden,et al.  Simultaneous edited MRS of GABA and glutathione , 2016, NeuroImage.

[55]  P. Luijten,et al.  Improved efficiency on editing MRS of lactate and γ‐aminobutyric acid by inclusion of frequency offset corrected inversion pulses at high fields , 2013, NMR in biomedicine.

[56]  Robin A. de Graaf.  In vivo NMR spectroscopy , 1998 .

[57]  Andrew Blamire,et al.  Human Auditory Cortex Neurochemistry Reflects the Presence and Severity of Tinnitus , 2015, The Journal of Neuroscience.

[58]  Carlo Caltagirone,et al.  GABA System in Schizophrenia and Mood Disorders: A Mini Review on Third-Generation Imaging Studies , 2016, Front. Psychiatry.

[59]  S. Provencher.  Automatic quantitation of localized in vivo 1H spectra with LCModel , 2001, NMR in biomedicine.

[60]  Rolf Gruetter,et al.  Net increase of lactate and glutamate concentration in activated human visual cortex detected with magnetic resonance spectroscopy at 7 tesla , 2013, Journal of neuroscience research.

[61]  K. Uğurbil,et al.  In vivo 1H NMR spectroscopy of the human brain at high magnetic fields: Metabolite quantification at 4T vs. 7T , 2009, Magnetic resonance in medicine.

[62]  Sanjay Kalra,et al.  Measurement of GABA and contaminants in gray and white matter in human brain in vivo , 2007, Magnetic resonance in medicine.

[63]  Reggie Taylor,et al.  Functional magnetic resonance spectroscopy of glutamate in schizophrenia and major depressive disorder: anterior cingulate activity during a color-word Stroop task , 2015, npj Schizophrenia.

[64]  T. Arndt,et al.  In vivo , 2019, Springer Reference Medizin.

[65]  G B Matson,et al.  A detailed analysis of localized J‐difference GABA editing: theoretical and experimental study at 4 T , 2008, NMR in biomedicine.

[66]  Arend Heerschap,et al.  Towards 1H-MRSI of the human brain at 7T with slice-selective adiabatic refocusing pulses , 2008, Magnetic Resonance Materials in Physics, Biology and Medicine.

[67]  G. Bloch,et al.  Brain GABA editing without macromolecule contamination , 2001, Magnetic resonance in medicine.

[68]  D. Graveron-Demilly,et al.  Java-based graphical user interface for the MRUI quantitation package , 2001, Magnetic Resonance Materials in Physics, Biology and Medicine.