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      Multi-Regional Investigation of the Relationship between Functional MRI Blood Oxygenation Level Dependent (BOLD) Activation and GABA Concentration

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          Abstract

          Several recent studies have reported an inter-individual correlation between regional GABA concentration, as measured by MRS, and the amplitude of the functional blood oxygenation level dependent (BOLD) response in the same region. In this study, we set out to investigate whether this coupling generalizes across cortex. In 18 healthy participants, we performed edited MRS measurements of GABA and BOLD-fMRI experiments using regionally related activation paradigms. Regions and tasks were the: occipital cortex with a visual grating stimulus; auditory cortex with a white noise stimulus; sensorimotor cortex with a finger-tapping task; frontal eye field with a saccade task; and dorsolateral prefrontal cortex with a working memory task. In contrast to the prior literature, no correlation between GABA concentration and BOLD activation was detected in any region. The origin of this discrepancy is not clear. Subtle differences in study design or insufficient power may cause differing results; these and other potential reasons for the discrepant results are discussed. This negative result, although it should be interpreted with caution, has a larger sample size than prior positive results, and suggests that the relationship between GABA and the BOLD response may be more complex than previously thought.

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          Most cited references28

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          Simultaneous in vivo spectral editing and water suppression.

          Water suppression is typically performed in vivo by exciting the longitudinal magnetization in combination with dephasing, or by using frequency-selective coherence generation. MEGA, a frequency-selective refocusing technique, can be placed into any pulse sequence element designed to generate a Hahn spin-echo or stimulated echo, to dephase transverse water coherences with minimal spectral distortions. Water suppression performance was verified in vivo using stimulated echo acquisition mode (STEAM) localization, which provided water suppression comparable with that achieved with four selective pulses in 3,1-DRYSTEAM. The advantage of the proposed method was exploited for editing J-coupled resonances. Using a double-banded pulse that selectively inverts a J-coupling partner and simultaneously suppresses water, efficient metabolite editing was achieved in the point resolved spectroscopy (PRESS) and STEAM sequences in which MEGA was incorporated. To illustrate the efficiency of the method, the detection of gamma-aminobutyric acid (GABA) was demonstrated, with minimal contributions from macromolecules and overlying singlet peaks at 4 T. The estimated occipital GABA concentration was consistent with previous reports, suggesting that editing for GABA is efficient when based on MEGA at high field strengths.
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            The Role of GABA in Human Motor Learning

            Results There is considerable variability in motor learning behavior across individuals [7], and the present study aimed to test whether some of this variability could be explained by variation in responsiveness of the GABA system, because GABA modulation plays an important role in learning [1–4]. As a measure of GABA responsiveness, we used magnetic resonance spectroscopy (MRS) to quantify changes in GABA concentration following anodal transcranial direct current stimulation (tDCS), a noninvasive technique that decreases GABA within the motor cortex [5], increases cortical excitability [8], and enhances short-term learning [9]. We predicted that individuals who show less tDCS-mediated GABA modulation would show less behavioral evidence of motor learning and less modulation of fMRI responses during learning. Subjects participated in three experimental sessions on different days. The first two sessions were MRS sessions, during which GABA-edited spectra were acquired before and after 10 min of tDCS. In the third session, subjects performed an explicit sequence learning task during fMRI, and no tDCS was applied. Motor Behavior Motor learning was assessed via change in reaction times to a visually cued explicit sequence learning task performed with the four fingers of the right hand during fMRI acquisition in session 3. All subjects showed a significant reduction in reaction times across successive learning blocks (Figure 1A; repeated-measures analysis of variance, main effect of BLOCK F(15,150) = 19.95; p  2.0 and a (corrected) cluster significance threshold of p = 0.01.
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              Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA.

              There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current 'state-of-the-art' in the field of GABA-edited MRS at 3T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 February 2015
                2015
                : 10
                : 2
                : e0117531
                Affiliations
                [1 ]The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, Maryland, United States of America
                [2 ]F. M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States of America
                [3 ]Department of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, Maryland, United States of America
                Brown University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ADH BAA JJP SY PBB RAEE. Performed the experiments: ADH NAJP. Analyzed the data: ADH RAEE. Contributed reagents/materials/analysis tools: ADH NAJP BAA SY JJP PBB RAEE. Wrote the paper: ADH NAJP BAA SY JJP PBB RAEE.

                Article
                PONE-D-14-29838
                10.1371/journal.pone.0117531
                4336183
                f47cea48-286c-43ab-89ac-0840bf7f4e11
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 7 July 2014
                : 6 December 2014
                Page count
                Figures: 4, Tables: 3, Pages: 17
                Funding
                This work was supported by National Institutes of Health grants R21 NS077300 to ADH, SY, JJP, PBB, RAEE, P41 EB015909 to JJP, PPB, RAEE, and R01 EB016089 to ADH, NAJP, PBB, RAEE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Ethical restrictions prevent public sharing of data. Requests for an ethically compliant dataset may be sent to Richard Edden (raee2@jhu.edu).

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