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Supplementary data for a focused review and meta-analysis of 1H-MRS studies on cerebral glutamate and GABA levels in high-risk of psychosis states.

ABSTRACT: Data (attached) for a focused review and meta-analysis of cerebral levels of glutamate, Glx, and GABA levels assessed with 1H-MRS in high-risk of psychosis states was collected and stored at covidence.org and extracted to The Cochrane Collaboration Review Manager software package (RevMan Version 5.3) for meta-analytical purposes. Meta-analyses were performed with a random-effects, inverse-variance weighted model to calculate the pooled effect size. Heterogeneity was measured using the I2 value. Significance was assessed using two-sided 95% confidence intervals. Potential publication bias was assessed by visual inspection of funnel plots. Supplementary to the co-submitted article are comprehensive meta-analyses of glutamate, Glx, and GABA, as well as the PRISMA flow diagram of included studies and a list of studies included in the review along with available measures and methodological variables. The attached data offers an insight into the included studies and the specified metabolite values for each study and offers possible further investigation for other researchers, as well as an insight into the review and meta-analyses performed. The supplementary material also serves to support findings and interpretations in the main article.

SUBMITTER: Wenneberg C

PROVIDER: S-EPMC6920491 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Supplementary data for a focused review and meta-analysis of <sup>1</sup>H-MRS studies on cerebral glutamate and GABA levels in high-risk of psychosis states.

Wenneberg Christina C Glenthøj Birte Yding BY Hjorthøj Carsten C Zingenberg Frederik Johan Buchardt FJB Glenthøj Louise Birkedal LB Rostrup Egill E Broberg Brian Villumsen BV Nordentoft Merete M

Data in brief 20191204

Data (attached) for a focused review and meta-analysis of cerebral levels of glutamate, Glx, and GABA levels assessed with <sup>1</sup>H-MRS in high-risk of psychosis states was collected and stored at covidence.org and extracted to The Cochrane Collaboration Review Manager software package (RevMan Version 5.3) for meta-analytical purposes. Meta-analyses were performed with a random-effects, inverse-variance weighted model to calculate the pooled effect size. Heterogeneity was measured using the ...[more]

PMID: 31886355

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Project description:Advances in functional magnetic resonance spectroscopy (fMRS) have enabled the quantification of activity-dependent changes in neurotransmitter concentrations in vivo. However, the physiological basis of the large changes in GABA and glutamate observed by fMRS (>10%) over short time scales of less than a minute remain unclear as such changes cannot be accounted for by known synthesis or degradation metabolic pathways. Instead, it has been hypothesized that fMRS detects shifts in neurotransmitter concentrations as they cycle from presynaptic vesicles, where they are largely invisible, to extracellular and cytosolic pools, where they are detectable. The present paper uses a computational modelling approach to demonstrate the viability of this hypothesis. A new mean-field model of the neural mechanisms generating the fMRS signal in a cortical voxel is derived. The proposed macroscopic mean-field model is based on a microscopic description of the neurotransmitter dynamics at the level of the synapse. Specifically, GABA and glutamate are assumed to cycle between three metabolic pools: packaged in the vesicles; active in the synaptic cleft; and undergoing recycling and repackaging in the astrocytic or neuronal cytosol. Computational simulations from the model are used to generate predicted changes in GABA and glutamate concentrations in response to different types of stimuli including pain, vision, and electric current stimulation. The predicted changes in the extracellular and cytosolic pools corresponded to those reported in empirical fMRS data. Furthermore, the model predicts a selective control mechanism of the GABA/glutamate relationship, whereby inhibitory stimulation reduces both neurotransmitters, whereas excitatory stimulation increases glutamate and decreases GABA. The proposed model bridges between neural dynamics and fMRS and provides a mechanistic account for the activity-dependent changes in the glutamate and GABA fMRS signals. Lastly, these results indicate that echo-time may be an important timing parameter that can be leveraged to maximise fMRS experimental outcomes.

Dataset Information

Supplementary data for a focused review and meta-analysis of 1H-MRS studies on cerebral glutamate and GABA levels in high-risk of psychosis states.

Publications

Supplementary data for a focused review and meta-analysis of <sup>1</sup>H-MRS studies on cerebral glutamate and GABA levels in high-risk of psychosis states.

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