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GABA, glutamate and neural activity: a systematic review with meta-analysis of multimodal 1H-MRS-fMRI studies

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posted on 2023-06-10, 00:01 authored by Amanda Kiemes, Cathy Davies, Matthew J Kempton, Paulina B Lukow, Carly Bennallick, James StoneJames Stone, Gemma Modinos
Multimodal neuroimaging studies combining proton magnetic resonance spectroscopy ( H-MRS) to quantify GABA and/or glutamate concentrations and functional magnetic resonance imaging (fMRI) to measure brain activity non-invasively have advanced understanding of how neurochemistry and neurophysiology may be related at a macroscopic level. The present study aimed to perform a systematic review and meta-analysis of available studies examining the relationship between H-MRS glutamate and/or GABA levels and task-related fMRI signal in the healthy brain. Ovid (Medline, Embase, and PsycINFO) and Pubmed databases were systematically searched to identify articles published until December 2019. The primary outcome of interest was the association between resting levels of glutamate or GABA and task-related fMRI. Fifty-five papers were identified for inclusion in the systematic review. A further 22 studies were entered into four separate meta-analyses. These meta-analyses found evidence of significant negative associations between local GABA levels and (a) fMRI activation to visual tasks in the occipital lobe, and (b) activation to emotion processing in the medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC). However, there was no significant association between mPFC/ACC glutamate levels and fMRI activation to cognitive control tasks or to emotional processing, with the relationship to emotion processing related neural activity narrowly missing significance. Moreover, our systematic review also found converging evidence of negative associations between GABA levels and local brain activity, and positive associations between glutamate levels and distal brain activity, outside of the H-MRS sampling region. Albeit less consistently, additional relationships between GABA levels and distal brain activity and between glutamate levels and local brain activity were found. It remains unclear if the absence of effects for other brain regions and other cognitive-emotional domains reflects study heterogeneity or potential confounding effects of age, sex, or other unknown factors. Advances in H-MRS methodology as well as in the integration of H-MRS readouts with other imaging modalities for indexing neural activity hold great potential to reveal key aspects of the pathophysiology of mental health disorders involving aberrant interactions between neurochemistry and neurophysiology such as schizophrenia. 1 1 1 1 1

History

Publication status

  • Published

File Version

  • Published version

Journal

Frontiers in Psychiatry

ISSN

1664-0640

Publisher

Frontiers Media

Volume

12

Page range

1-24

Article number

a644315

Event location

Switzerland

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-06-03

First Open Access (FOA) Date

2021-06-03

First Compliant Deposit (FCD) Date

2021-06-03

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