Neurotransmitter changes during interference task in anterior cingulate cortex: evidence from fMRI-guided functional MRS at 3 T

Neural activity as indirectly observed in blood oxygenation level-dependent (BOLD) response is thought to reflect changes in neurotransmitter flux. In this study, we used fMRI-guided functional magnetic resonance spectroscopy (MRS) to measure metabolite/BOLD associations during a cognitive task at 3 T. GABA and glutamate concentration in anterior cingulate cortex (ACC) were determined by means of MRS using the SPECIAL pulse sequence before, during and after the performance of a manual Stroop task. MRS voxel positions were centred around individuals’ BOLD activity during Stroop performance. Levels of GABA and glutamate showed inverted U-shape patterns across measurement time points (before, during, and after task), glutamine increased linearly and total creatine did not change. The GABA increase during task performance was associated with ACC BOLD signal changes in both congruent and incongruent Stroop conditions. Using an fMRI-guided MRS approach, an association between induced inhibitory neurotransmitter increase and BOLD changes was observed. The proposed procedure might allow the in vivo investigation of normal and dysfunctional associations between neurotransmitters and BOLD signal crucial for cerebral functioning.

[1]  G F Mason,et al.  Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. , 1999, Archives of general psychiatry.

[2]  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.

[3]  S. Provencher.  Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[4]  E. Pace-Schott,et al.  Cortical GABA levels in primary insomnia. , 2012, Sleep.

[5]  P. Boesiger,et al.  GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI , 2007, Nature Neuroscience.

[6]  Derek K. Jones,et al.  Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans , 2009, Proceedings of the National Academy of Sciences.

[7]  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.

[8]  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.

[9]  P. Matthews,et al.  Polarity-Sensitive Modulation of Cortical Neurotransmitters by Transcranial Stimulation , 2009, The Journal of Neuroscience.

[10]  Peter Jezzard,et al.  Baseline GABA concentration and fMRI response , 2010, NeuroImage.

[11]  K. Dobson,et al.  A systematic meta-analysis of the Stroop task in depression. , 2012, Clinical psychology review.

[12]  Roger J. Ordidge,et al.  Image selected in-vivo spectroscopy (ISIS) , 1985 .

[13]  Xi-Nian Zuo,et al.  REST: A Toolkit for Resting-State Functional Magnetic Resonance Imaging Data Processing , 2011, PloS one.

[14]  M. Botvinick,et al.  Anterior cingulate cortex, error detection, and the online monitoring of performance. , 1998, Science.

[15]  Rolf Gruetter,et al.  Localized short‐echo‐time proton MR spectroscopy with full signal‐intensity acquisition , 2006, Magnetic resonance in medicine.

[16]  Marzena Wylezinska,et al.  Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients. , 2008, The international journal of neuropsychopharmacology.

[17]  Irene Neuner,et al.  GABA Concentration in Posterior Cingulate Cortex Predicts Putamen Response during Resting State fMRI , 2014, PloS one.

[18]  P. Matthews,et al.  Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning. , 2006, Journal of neurophysiology.

[19]  J. Jonides,et al.  Interference resolution: Insights from a meta-analysis of neuroimaging tasks , 2007, Cognitive, affective & behavioral neuroscience.

[20]  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.

[21]  Fahmeed Hyder,et al.  Reduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy , 1999 .

[22]  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.

[23]  D. Meyerhoff,et al.  Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. , 2014, Sleep.

[24]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[25]  Gereon R. Fink,et al.  Modulatory Effects of Levodopa on Cognitive Control in Young but not in Older Subjects: A Pharmacological fMRI Study , 2011, Journal of Cognitive Neuroscience.

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

[27]  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.

[28]  G. Hasler,et al.  Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: Preliminary findings , 2014, Psychiatry Research: Neuroimaging.

[29]  C. Carter,et al.  Anterior cingulate cortex and conflict detection: An update of theory and data , 2007, Cognitive, affective & behavioral neuroscience.

[30]  J. Krystal,et al.  Increased cortical GABA concentrations in depressed patients receiving ECT. , 2003, The American journal of psychiatry.

[31]  P. Jezzard,et al.  Neurochemical Effects of Theta Burst Stimulation as Assessed by Magnetic Resonance Spectroscopy , 2009, Journal of neurophysiology.

[32]  Melissa R. Weiner,et al.  INSULA AND ANTERIOR CINGULATE GABA LEVELS IN POSTTRAUMATIC STRESS DISORDER: PRELIMINARY FINDINGS USING MAGNETIC RESONANCE SPECTROSCOPY , 2014, Depression and anxiety.

[33]  S. A. Wijtenburg,et al.  In vivo measurements of glutamate, GABA, and NAAG in schizophrenia. , 2013, Schizophrenia bulletin.

[34]  P. Dayan,et al.  Differential, but not opponent, effects of l-DOPA and citalopram on action learning with reward and punishment , 2013, Psychopharmacology.

[35]  Mark Hallett,et al.  Impulsive choice and response in dopamine agonist-related impulse control behaviors , 2009, Psychopharmacology.

[36]  John H Krystal,et al.  Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. , 2004, Archives of general psychiatry.

[37]  Jonathan D. Cohen,et al.  Conflict monitoring and anterior cingulate cortex: an update , 2004, Trends in Cognitive Sciences.

[38]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[39]  J. Krystal,et al.  Impairment of GABAergic transmission in depression: new insights from neuroimaging studies. , 2000, Critical reviews in neurobiology.

[40]  Jürgen Gallinat,et al.  Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla , 2004, NeuroImage.

[41]  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.

[42]  Kathryn M. McMillan,et al.  A comparison of label‐based review and ALE meta‐analysis in the Stroop task , 2005, Human brain mapping.

[43]  Rita Z. Goldstein,et al.  Methylphenidate enhances executive function and optimizes prefrontal function in both health and cocaine addiction. , 2014, Cerebral cortex.

[44]  Roger J. Ordidge,et al.  Image-selected in Vivo spectroscopy (ISIS). A new technique for spatially selective nmr spectroscopy , 1986 .

[45]  R. Yoshimura,et al.  Reduction of brain γ-aminobutyric acid (GABA) concentrations in early-stage schizophrenia patients: 3T Proton MRS study , 2009, Schizophrenia Research.

[46]  J. Ridley.  Studies of Interference in Serial Verbal Reactions , 2001 .

[47]  R. Shulman,et al.  The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[48]  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.

[49]  Georg Northoff,et al.  Associations of regional GABA and glutamate with intrinsic and extrinsic neural activity in humans—A review of multimodal imaging studies , 2014, Neuroscience & Biobehavioral Reviews.

[50]  Jong H. Yoon,et al.  GABA Concentration Is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression , 2010, The Journal of Neuroscience.

[51]  R. Kahn,et al.  Region and state specific glutamate downregulation in major depressive disorder: A meta-analysis of 1H-MRS findings , 2012, Neuroscience & Biobehavioral Reviews.

[52]  Gregor Hasler,et al.  Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. , 2007, Archives of general psychiatry.

[53]  A. Schousboe,et al.  Neuronal-astrocytic interactions in glutamate metabolism. , 1993, Biochemical Society transactions.

[54]  Rolf Gruetter,et al.  Unedited in vivo detection and quantification of γ‐aminobutyric acid in the occipital cortex using short‐TE MRS at 3 T , 2013, NMR in biomedicine.

[55]  D. Plante,et al.  Reduced γ-Aminobutyric Acid in Occipital and Anterior Cingulate Cortices in Primary Insomnia: a Link to Major Depressive Disorder? , 2012, Neuropsychopharmacology.

[56]  D. Weinberger,et al.  Genes, dopamine and cortical signal-to-noise ratio in schizophrenia , 2004, Trends in Neurosciences.

[57]  J. Krystal,et al.  Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. , 2002, The American journal of psychiatry.

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

[59]  Xiao-Jing Wang.  Neurophysiological and computational principles of cortical rhythms in cognition. , 2010, Physiological reviews.

[60]  Mark Slifstein,et al.  Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. , 2012, Archives of general psychiatry.

[61]  Peter B Barker,et al.  Measuring T2 in vivo with J‐difference editing: Application to GABA at 3 tesla , 2012, Journal of magnetic resonance imaging : JMRI.

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

[63]  Daniel Brandeis,et al.  Frontal GABA Levels Change during Working Memory , 2012, PloS one.