A comprehensive guide to MEGA-PRESS for GABA measurement.

The aim of this guideline is to provide a series of evidence-based recommendations that allow those new to using MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats. The guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesized and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds. The final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel. These 23 expert-reviewed recommendations and accompanying extended documentation form a readily useable guideline to allow those new to using MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data.

Effect of Age on GABA+ and Glutathione in a Pediatric Sample.

BACKGROUND AND PURPOSE: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the human brain and is implicated in several neuropathologies. Glutathione is a major antioxidant in the brain and is considered a marker of oxidative stress. Several studies have reported age-related declines in GABA levels in adulthood, but the trajectory of both GABA and glutathione during childhood has not been well explored. The aim of this study is to establish how GABA and glutathione vary with age during early development. MATERIALS AND METHODS: Twenty-three healthy children (5.6-13.9 years of age) were recruited for this study. MR imaging/MR spectroscopy experiments were conducted on a 3T MR scanner. A 27-mL MR spectroscopy voxel was positioned in the frontal lobe. J-difference edited MR spectroscopy was used to spectrally edit GABA and glutathione. Data were analyzed using the Gannet software, and GABA+ (GABA + macromolecules/homocarnosine) and glutathione were quantified using water (GABA+H2O and GlutathioneH2O) and Cr (GABA+/Cr and glutathione/Cr) as concentration references. Also, the relative gray matter contribution to the voxel volume (GMratio) was estimated from structural images. Pearson correlation coefficients were used to examine the association between age and GABA+H2O (and glutathioneH2O), between age and GABA+/Cr (and glutathione/Cr), and between age and GMratio. RESULTS: Both GABA+H2O (r = 0.63, P = .002) and GABA+/Cr (r = 0.48, P = .026) significantly correlated with age, whereas glutathione measurements and GMratio did not. CONCLUSIONS: We demonstrate increases in GABA and no differences in glutathione with age in a healthy pediatric sample. This study provides insight into neuronal maturation in children and may facilitate better understanding of normative behavioral development and the pathophysiology of developmental disorders.

GABA-from Inhibition to Cognition: Emerging Concepts.

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.

Structural changes in brain morphology induced by brief periods of repetitive sensory stimulation.

There is a growing interest in identifying the neural mechanisms by which the human brain allows for improving performance. Tactile perceptual measurements, e.g. two-point discrimination (2ptD), can be used to investigate neural mechanisms of perception as well as perceptual improvement. Improvement can be induced in a practice-independent manner, e.g. in the tactile domain through repetitive somatosensory stimulation (rSS). With respect to tactile perception, the role of cortical excitability and activation within the somatosensory cortex has been investigated extensively. However, the role of structural properties, such as regional gray matter (GM) volume, is unknown. Using high resolution imaging and voxel-based morphometry (VBM), we sought to investigate how regional GM volume relates to individual 2ptD performance. Furthermore, we wanted to determine if electrical rSS has an influence on regional GM volume. 2ptD thresholds of the index fingers were assessed bilaterally. High-resolution (1 mm3), T1-weighted images were obtained using a 3T scanner pre-and post-stimulation. RSS was applied for 45 min to the dominant right hand, specifically to the fingertips of all fingers. At baseline, performance in the 2ptD task was associated with regional GM volume in the thalamus, primary somatosensory cortex, and primary visual cortex (negative association). After 45 min of rSS, we observed an improvement in 2ptD of the stimulated hand, whereas no improvement in tactile performance was seen on the non-stimulated side. These perceptual changes were accompanied by an increase in GM volume in the left somatosensory cortex and the degree of improvement correlated with GM volume changes in the insular cortex. Our results show that structural changes in the brain, specifically in regions receiving afferent input from the stimulated body site can be induced via a short-term intervention lasting only 45 min. However, the neurobiological correlates of these changes and the dynamics need to be further elucidated.