Abstract
Multimodal neuroimaging studies combining proton magnetic resonance spectroscopy (1H-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 1H-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 1H-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 1H-MRS methodology as well as in the integration of 1H-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.
Highlights
METHODSExcitation-inhibition balance plays a major role in determining neural activity (1)
This investigation has been achieved through the development and optimisation of neuroimaging techniques enabling quantification of GABA and glutamate concentrations via proton magnetic resonance spectroscopy (1H-MRS), and of neural activation via measurement of blood oxygen level dependent (BOLD) signal with functional magnetic resonance imaging
The authors reported that GABA levels were related to reduced positive BOLD response or reduced negative BOLD response (NBR) within the same brain region, while glutamate levels were more commonly related to inter-regional neural responses
Summary
METHODSExcitation-inhibition balance plays a major role in determining neural activity (1). The influence of the brain’s major excitatory and inhibitory neurotransmitters [glutamate and γ-aminobutyric acid (GABA)], on neural activity has been studied in detail [see Isaacson and Scanziani (1), Lauritzen et al (2)]. This investigation has been achieved through the development and optimisation of neuroimaging techniques enabling quantification of GABA and glutamate concentrations via proton magnetic resonance spectroscopy (1H-MRS), and of neural activation via measurement of blood oxygen level dependent (BOLD) signal with functional magnetic resonance imaging (fMRI). A previous narrative review by Duncan et al (4) sought to address this question with a comprehensive overview of studies using imaging techniques such as magnetoencephalography, electroencephalography, fMRI, positron emission tomography and 1H-MRS, as well as behavioural measures as proxies for neural activity and pharmaceutical manipulations of neurotransmitter levels. More recent reports outside of the previous review include studies on regions of interest that had previously been examined too infrequently to permit meta-analysis, providing important insights into the nature of neurochemistry-neurophysiology associations in a variety of brain regions and task domains
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
