Brain GABA and glutamate levels across pain conditions: A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool

Peek, Aimie L.; Rebbeck, Trudy; Puts, Nicolaas A.J.; Watson, Julia; Aguila, Maria-Eliza R.; Leaver, Andrew

doi:10.1016/j.neuroimage.2020.116532

Cited by 115 publications

(126 citation statements)

References 93 publications

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“…In addition to higher glutamate, a recent systematic review demonstrated that adults with migraine showed higher levels of GABA in various cortical and sub-cortical regions. 46 In the thalamus, we found GABA/Glx to be higher in Migraine, primarily driven by higher GABA, although group comparisons did not reach statistical significance. Within the migraine group, we found an association between higher GABA levels and higher migraine burden (measured by the PedMIDAS) in all three areas (although only the sensorimotor cortex reached statistical significance), indicating that children with higher GABA levels are more affected by their migraines.…”

Section: Discussioncontrasting

confidence: 63%

Gaba and Glutamate Changes in Pediatric Migraine

Bell

Stokoe

Khaira

et al. 2020

Preprint

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Despite migraine being one of the top five most prevalent childhood diseases, a lack of knowledge about pediatric migraine limits effective treatment strategies; standard adult pharmaceutical therapies are less effective in children and can carry undesirable side-effects. Non-pharmacological therapies have shown some success in adults; however, to appropriately apply these in children we need to understand pediatric migraine's underlying biology. One theory is that migraine results from an imbalance in cortical excitability. Magnetic resonance spectroscopy (MRS) studies show changes in GABA and glutamate levels (the primary inhibitory and excitatory neurotransmitters in the brain, respectively) in multiple brain regions. Although there is indirect evidence of abnormal excitability in pediatric migraine, GABA and glutamate levels have yet to be assessed.The purpose of this study was to measure levels of GABA and glutamate in the thalamus, sensorimotor cortex and visual cortex of children with migraine using MRS. We found that children with migraine and aura had significantly lower glutamate levels in the visual cortex as compared to control children, opposite to results seen in adults. Additionally, we found significant correlations between metabolite levels and migraine characteristics; higher GABA levels were associated with a higher migraine burden. We also found that higher glutamate in the thalamus and higher GABA/Glx ratios in the sensorimotor cortex were associated with duration since diagnosis, i.e., having migraines longer. Lower GABA levels in the sensorimotor cortex were associated with being closer to their next migraine attack. Together this indicates that GABA and glutamate disturbances occur early in migraine pathophysiology and emphasizes that evidence from adults with migraine cannot be immediately translated to paediatric sufferers. This highlights the need for further mechanistic studies of migraine in children, to aid in the development of more effective treatments.

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Section: Discussioncontrasting

confidence: 63%

Gaba and Glutamate Changes in Pediatric Migraine

Bell

Stokoe

Khaira

et al. 2020

Preprint

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“…MR data were acquired on a Philips Achieva 3 Tesla scanner, with a 32-channel highresolution head coil, over two scanning sessions. Detailed methods were reported in recent publications from our group [Schallmo et al, 2018; and are briefly described here following the MRS-Q guidelines for reporting acquisition parameters and quality measures of MRS [Peek et al, 2020]. Briefly, we used Mescher-Garwood Point Resolved Spectroscopy sequence (MEGA-PRESS) to quantify GABA+ and Glx within 27 cm 3 voxels (320 averages, 2 s TR, 68 ms TE, 2048 spectral data points, 2 kHz spectral width, 1.4 kHz refocusing pulse, VAPOR water suppression).…”

Section: Mri and Mrs Acquisitionmentioning

confidence: 99%

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

et al. 2020

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The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter γaminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined

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“…A third step was performed to assess whether studies adhered to consensus quality assurance criteria for data collection, analysis, and reporting. For this purpose, two coauthors (NP and EP) evaluated all remaining studies using the MRS-Q, which was specifically designed for MRS and based upon consensus documentation (Peek et al, 2020).…”

Section: Data Qualitymentioning

confidence: 99%

“…The most widely used edited MRS technique is MEGA-PRESS (Mescher et al, 1998), in which a GABA-selective editing pulse at 1.9 ppm is applied in half of the experiment (edit-ON). Due to its low concentration, measurement of the GABAedited signal in humans requires a large voxel (most commonly 27 cm3 Mullins et al, 2014;Peek et al, 2020;Salthouse, 2010) to keep acquisition times reasonable (10 minutes) and to provide an adequate signal-to-noise ratio (Mikkelsen et al, 2018). This limitation constrains the spatial specificity of the measurement to coarse regions that often lack discrete functional specificity.…”

mentioning

confidence: 99%

The trajectory of cortical GABA levels across the lifespan: An individual participant data meta-analysis of edited MRS studies

Porges

Jensen

Foster

et al. 2020

Preprint

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GABA is the principal inhibitory neurotransmitter in the human brain and can be measured with Magnetic Resonance Spectroscopy (MRS). Conflicting accounts report decreases and increases in cortical GABA levels across the lifespan. This incompatibility may be an artifact of the size and age-range of the samples utilized in these studies. No single study to date has included the entire lifespan. In this study, 8 suitable datasets were integrated to generate a model of the trajectory of GABA across the lifespan. Data were fit using both a log-normal curve and a nonparametric spline as regression models using a multi-level Bayesian model utilizing the Stan language. Integrated data show the lifespan trajectory of GABA involves an early period of rapid increase, followed by a period of stability during early adulthood, with a gradual decrease during adulthood and aging that is described well by both spline and log-normal models. The information gained will provide a general framework to inform expectations of future studies based on the age of the population being studied.

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Brain GABA and glutamate levels across pain conditions: A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool

Cited by 115 publications

References 93 publications

Gaba and Glutamate Changes in Pediatric Migraine

Gaba and Glutamate Changes in Pediatric Migraine

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

The trajectory of cortical GABA levels across the lifespan: An individual participant data meta-analysis of edited MRS studies

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