Kiemes Amanda, Davies Cathy, Kempton Matthew J, Lukow Paulina B, Bennallick Carly, Stone James M, Modinos Gemma
Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Front Psychiatry. 2021 Mar 8;12:644315. doi: 10.3389/fpsyt.2021.644315. eCollection 2021.
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.
多模态神经影像学研究结合质子磁共振波谱（H-MRS）来量化γ-氨基丁酸（GABA）和/或谷氨酸浓度，并利用功能磁共振成像（fMRI）来无创测量大脑活动，这推进了我们对神经化学和神经生理学在宏观层面上如何关联的理解。本研究旨在对现有研究进行系统综述和荟萃分析，这些研究探讨了健康大脑中H-MRS谷氨酸和/或GABA水平与任务相关fMRI信号之间的关系。我们系统检索了Ovid（包括医学期刊数据库Medline、Embase和心理学文摘数据库PsycINFO）和PubMed数据库，以识别截至2019年12月发表的文章。感兴趣的主要结果是谷氨酸或GABA的静息水平与任务相关fMRI之间的关联。共识别出55篇论文纳入系统综述。另有22项研究被纳入四项独立的荟萃分析。这些荟萃分析发现，局部GABA水平与（a）枕叶视觉任务的fMRI激活，以及（b）内侧前额叶皮质（mPFC）/前扣带回皮质（ACC）情绪处理的激活之间存在显著负相关的证据。然而，mPFC/ACC谷氨酸水平与认知控制任务或情绪处理的fMRI激活之间没有显著关联，与情绪处理相关神经活动的关系勉强未达到显著水平。此外，我们的系统综述还发现，在H-MRS采样区域之外，GABA水平与局部大脑活动之间存在负相关、谷氨酸水平与远端大脑活动之间存在正相关的趋同证据。虽然不太一致，但也发现了GABA水平与远端大脑活动之间以及谷氨酸水平与局部大脑活动之间的其他关系。目前尚不清楚其他脑区和其他认知-情感领域缺乏效应是反映了研究的异质性，还是年龄、性别或其他未知因素的潜在混杂效应。H-MRS方法学的进展以及将H-MRS读数与其他成像模态整合以索引神经活动，对于揭示涉及神经化学和神经生理学异常相互作用的精神健康障碍（如精神分裂症）病理生理学的关键方面具有巨大潜力。
