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 3 T 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.

Functional imaging of the human brain is an increasingly important technique for clinical and cognitive neuroscience research, with functional MRI (fMRI) of the blood oxygen level-dependent (BOLD) response and electroencephalography or magnetoencephalography (MEG) recordings of neural oscillations being 2 of the most popular approaches. However, the neural and physiological mechanisms that generate these responses are only partially understood and sources of interparticipant variability in these measures are rarely investigated. Here, we test the hypothesis that the properties of these neuroimaging metrics are related to individual levels of cortical inhibition by combining magnetic resonance spectroscopy to quantify resting GABA concentration in the visual cortex, MEG to measure stimulus-induced visual gamma oscillations and fMRI to measure the BOLD response to a simple visual grating stimulus. Our results demonstrate that across individuals gamma oscillation frequency is positively correlated with resting GABA concentration in visual cortex (R ‫؍‬ 0.68; P < 0.02), BOLD magnitude is inversely correlated with resting GABA (R ‫؍‬ ؊0.64; P < 0.05) and that gamma oscillation frequency is strongly inversely correlated with the magnitude of the BOLD response (R ‫؍‬ ؊0.88; P < 0.001). Our results are therefore supportive of recent theories suggesting that these functional neuroimaging metrics are dependent on the excitation/inhibition balance in an individual's cortex and have important implications for the interpretation of functional imaging results, particularly when making between-group comparisons in clinical research.functional magnetic resonance imaging ͉ magnetic resonance spectroscopy ͉ magnetoencephalography ͉ oscillations T he high spatial resolution and noninvasive nature of blood oxygen level-dependent (BOLD) functional MRI (fMRI) (1) have led to it becoming one of the most popular tools for measuring brain function in human neuroscience. However, fMRI provides only an indirect measure of neural activity by measuring task-related changes in cerebral haemodynamics that are coupled by a complex and only partially understood mechanism to changes in underlying neural activity. Recent evidence suggests that oscillations in the gamma frequency range, loosely defined as approximately 30-100 Hz, are well correlated temporally, spatially, and functionally with haemodynamic changes in cortex, suggesting a close relationship with the BOLD response (2-6). There is also increasing evidence that the most plausible mechanism for the generation of gamma oscillations is a neuronal network containing a mixture of interconnected pyramidal cells and GABAergic inhibitory interneurons (7-10) with the balance of excitation-inhibition setting the peak gamma oscillation frequency of the network (11). Similarly, it has recently been argued that the magnitude of the BOLD response is also sensitive to this excitation-inhibition balance (12, 13).In the current study, we tested the hypothesis that the local level of inhibition in an i...

Chemical exchange saturation transfer (CEST) is a magnetization transfer (MT) technique to indirectly detect pools of exchangeable protons through the water signal. CEST MRI has focused predominantly on signals from exchangeable protons downfield (higher frequency) from water in the CEST spectrum. Low power radiofrequency (RF) pulses can slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC). When doing so, saturation-transfer signals are revealed upfield from water, which is the frequency range of non-exchangeable aliphatic and olefinic protons. The visibility of such signals indicates the presence of a relayed transfer mechanism to the water signal, while their finite width reflects that these signals are likely due to mobile solutes. It is shown here in protein phantoms and the human brain that these signals build up slower than conventional CEST, at a rate typical for intramolecular nuclear Overhauser enhancement (NOE) effects in mobile macromolecules such as proteins/peptides and lipids. These NOE-based saturation transfer signals show a pH dependence, suggesting that this process is the inverse of the well-known exchange-relayed NOEs in high resolution NMR protein studies, thus an relayed-NOE CEST process. When studying 6 normal volunteers with a low-power pulsed CEST approach, the relayed-NOE CEST effect was about twice as large as the CEST effects downfield and larger in white matter than gray matter. This NOE contrast upfield from water provides a way to study mobile macromolecules in tissue. First data on a tumor patient show reduction in both relayed NOE and CEST amide proton signals leading to an increase in magnetization transfer ratio asymmetry, providing insight into previously reported amide proton transfer (APT) effects in tumors.