Dynamics of γ-aminobutyric Acid Concentration in the Human Brain in Response to Short Visual Stimulation

Overview

Journal MAGMA

Publisher Springer

Date 2023 Sep 16

PMID 37715877

Authors

Alexey Yakovlev

Alexandra Gritskova

Andrei Manzhurtsev

Maxim Ublinskiy

Petr Menshchikov

Anatoly Vanin

Dmitriy Kupriyanov

Tolib Akhadov

Natalia Semenova

Affiliations

Soon will be listed here.

Abstract

Objective: To find a possible quantitative relation between activation-induced fast (< 10 s) changes in the γ-aminobutyric acid (GABA) level and the amplitude of a blood oxygen level-dependent contrast (BOLD) response (according to magnetic resonance spectroscopy [MRS] and functional magnetic resonance imaging [fMRI]).

Materials And Methods: fMRI data and MEGA-PRESS magnetic resonance spectra [echo time (TE)/repetition time (TR) = 68 ms/1500 ms] of an activated area in the visual cortex of 33 subjects were acquired using a 3 T MR scanner. Stimulation was performed by presenting an image of a flickering checkerboard for 3 s, repeated with an interval of 13.5 s. The time course of GABA and creatine (Cr) concentrations and the width and height of resonance lines were obtained with a nominal time resolution of 1.5 s. Changes in the linewidth and height of n-acetylaspartate (NAA) and Cr signals were used to determine the BOLD effect.

Results: In response to the activation, the BOLD-corrected GABA + /Cr ratio increased by 5.0% (q = 0.027) and 3.8% (q = 0.048) at 1.6 and 3.1 s, respectively, after the start of the stimulus. Time courses of Cr and NAA signal width and height reached a maximum change at the 6th second (~ 1.2-1.5%, q < 0.05).

Conclusion: The quick response of the observed GABA concentration to the short stimulus is most likely due to a release of GABA from vesicles followed by its packaging back into vesicles.

References

Kim S, Ogawa S . Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab. 2012; 32(7):1188-206. PMC: 3390806. DOI: 10.1038/jcbfm.2012.23. View

Ogawa S, Lee T, Kay A, Tank D . Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A. 1990; 87(24):9868-72. PMC: 55275. DOI: 10.1073/pnas.87.24.9868. View

Logothetis N . The underpinnings of the BOLD functional magnetic resonance imaging signal. J Neurosci. 2003; 23(10):3963-71. PMC: 6741096. View

Attwell D, Buchan A, Charpak S, Lauritzen M, MacVicar B, Newman E . Glial and neuronal control of brain blood flow. Nature. 2010; 468(7321):232-43. PMC: 3206737. DOI: 10.1038/nature09613. View

Stanley J, Raz N . Functional Magnetic Resonance Spectroscopy: The "New" MRS for Cognitive Neuroscience and Psychiatry Research. Front Psychiatry. 2018; 9:76. PMC: 5857528. DOI: 10.3389/fpsyt.2018.00076. View

Koush Y, Rothman D, Behar K, de Graaf R, Hyder F . Human brain functional MRS reveals interplay of metabolites implicated in neurotransmission and neuroenergetics. J Cereb Blood Flow Metab. 2022; 42(6):911-934. PMC: 9125492. DOI: 10.1177/0271678X221076570. View

Pasanta D, He J, Ford T, Oeltzschner G, Lythgoe D, Puts N . Functional MRS studies of GABA and glutamate/Glx - A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022; 144:104940. PMC: 9846867. DOI: 10.1016/j.neubiorev.2022.104940. View

Muthukumaraswamy S, Edden R, Jones D, Swettenham J, Singh K . Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans. Proc Natl Acad Sci U S A. 2009; 106(20):8356-61. PMC: 2688873. DOI: 10.1073/pnas.0900728106. View

Mangia S, Tkac I, Gruetter R, Van de Moortele P, Giove F, Maraviglia B . Sensitivity of single-voxel 1H-MRS in investigating the metabolism of the activated human visual cortex at 7 T. Magn Reson Imaging. 2006; 24(4):343-8. DOI: 10.1016/j.mri.2005.12.023. View

10.

Donahue M, Near J, Blicher J, Jezzard P . Baseline GABA concentration and fMRI response. Neuroimage. 2010; 53(2):392-8. DOI: 10.1016/j.neuroimage.2010.07.017. View

11.

Lipp I, Evans C, Lewis C, Murphy K, Wise R, Caseras X . The relationship between fearfulness, GABA+, and fear-related BOLD responses in the insula. PLoS One. 2015; 10(3):e0120101. PMC: 4374765. DOI: 10.1371/journal.pone.0120101. View

12.

Michou E, Williams S, Vidyasagar R, Downey D, Mistry S, Edden R . fMRI and MRS measures of neuroplasticity in the pharyngeal motor cortex. Neuroimage. 2015; 117:1-10. PMC: 4828970. DOI: 10.1016/j.neuroimage.2015.05.007. View

13.

Bednarik P, Tkac I, Giove F, DiNuzzo M, Deelchand D, Emir U . Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla. J Cereb Blood Flow Metab. 2015; 35(4):601-10. PMC: 4420878. DOI: 10.1038/jcbfm.2014.233. View

14.

Mangia S, Tkac I, Gruetter R, Van de Moortele P, Maraviglia B, Ugurbil K . Sustained neuronal activation raises oxidative metabolism to a new steady-state level: evidence from 1H NMR spectroscopy in the human visual cortex. J Cereb Blood Flow Metab. 2006; 27(5):1055-63. DOI: 10.1038/sj.jcbfm.9600401. View

15.

Chen C, Sigurdsson H, Pepes S, Auer D, Morris P, Morgan P . Activation induced changes in GABA: Functional MRS at 7T with MEGA-sLASER. Neuroimage. 2017; 156:207-213. DOI: 10.1016/j.neuroimage.2017.05.044. View

16.

Schaller B, Xin L, OBrien K, Magill A, Gruetter R . Are glutamate and lactate increases ubiquitous to physiological activation? A (1)H functional MR spectroscopy study during motor activation in human brain at 7Tesla. Neuroimage. 2014; 93 Pt 1:138-45. DOI: 10.1016/j.neuroimage.2014.02.016. View

17.

Schubert F, Kuhn S, Gallinat J, Mekle R, Ittermann B . Towards a neurochemical profile of the amygdala using short-TE H magnetic resonance spectroscopy at 3 T. NMR Biomed. 2017; 30(5). DOI: 10.1002/nbm.3685. View

18.

Ip I, Berrington A, Hess A, Parker A, Emir U, Bridge H . Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain. Neuroimage. 2017; 155:113-119. PMC: 5519502. DOI: 10.1016/j.neuroimage.2017.04.030. View

19.

Kupers R, Danielsen E, Kehlet H, Christensen R, Thomsen C . Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex in man. Pain. 2009; 142(1-2):89-93. DOI: 10.1016/j.pain.2008.12.008. View

20.

Cleve M, Gussew A, Reichenbach J . In vivo detection of acute pain-induced changes of GABA+ and Glx in the human brain by using functional 1H MEGA-PRESS MR spectroscopy. Neuroimage. 2014; 105:67-75. DOI: 10.1016/j.neuroimage.2014.10.042. View