Relationship Between Cortical Excitation and Inhibition and Task-Induced Activation and Deactivation: A Combined Magnetic Resonance Spectroscopy and Functional Magnetic Resonance Imaging Study at 7T in First-Episode Psychosis

Overview

Journal Biol Psychiatry Cogn Neurosci Neuroimaging

Specialties Neurology
Psychiatry
Radiology

Date 2018 Nov 25

PMID 30470582

Citations 19

Authors

Gregory Overbeek

Timothy J Gawne

Meredith A Reid

Nouha Salibi

Nina V Kraguljac

David M White

Adrienne C Lahti

Affiliations

Soon will be listed here.

Abstract

Background: Schizophrenia is thought to be a disorder of brain dysconnectivity. An imbalance between cortical excitation/inhibition is also implicated, but the link between these abnormalities remains unclear. The present study used magnetic resonance spectroscopy and functional magnetic resonance imaging at 7T to investigate how measurements of glutamate and gamma-aminobutyric acid (GABA) relate to the blood oxygen level-dependent (BOLD) response during a cognitive task, and how these relationships are altered in schizophrenia.

Methods: Usable functional magnetic resonance imaging data from 17 first-episode psychosis (FEP) patients (4 women, 13 men) and 21 matched healthy control subjects (HCs) (5 women, 16 men) were acquired during a Stroop task. Within- and between-group comparisons of the BOLD response were performed. Neurometabolite levels were measured in the dorsal anterior cingulate cortex. Two multiple regressions investigated how glutamate, glutamine, and GABA related to the BOLD response in HCs and FEP patients separately. A third investigated between-group differences in the relationships between the BOLD response and each of these neurometabolites.

Results: Compared with HCs, FEP patients showed an increased BOLD response within regions of the executive and default mode networks. In FEP patients, the relationship between anterior cingulate cortex glutamate levels and the BOLD response in regions of the posterior default mode network was opposite to that of HCs. In FEP patients but not HCs, anterior cingulate cortex GABA levels correlated with the local BOLD response and with the Stroop reaction time.

Conclusion: These results suggest a mechanism whereby alterations in the relationship between cortical glutamate/GABA and BOLD response is disrupting the dynamic of major neural networks, possibly affecting cognition.

Citing Articles

Leveraging ultra-high field (7T) MRI in psychiatric research.

Calabro F, Parr A, Sydnor V, Hetherington H, Prasad K, Ibrahim T Neuropsychopharmacology. 2024; 50(1):85-102.

PMID: 39251774 PMC: 11525672. DOI: 10.1038/s41386-024-01980-6.

Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naïve first episode psychosis patients.

Maximo J, Briend F, Armstrong W, Kraguljac N, Lahti A Transl Psychiatry. 2024; 14(1):183.

PMID: 38600117 PMC: 11006887. DOI: 10.1038/s41398-024-02854-7.

Association of default-mode network neurotransmitters and inter-network functional connectivity in first episode psychosis.

Chen X, Song X, Ongur D, Du F Neuropsychopharmacology. 2023; 48(5):781-788.

PMID: 36788375 PMC: 10066209. DOI: 10.1038/s41386-023-01546-y.

Ultra-high field neuroimaging in psychosis: A narrative review.

Lavigne K, Kanagasabai K, Palaniyappan L Front Psychiatry. 2022; 13:994372.

PMID: 36506432 PMC: 9730890. DOI: 10.3389/fpsyt.2022.994372.

Neurometabolic and functional changes of default-mode network relate to clinical recovery in first-episode psychosis patients: A longitudinal H-MRS and fMRI study.

Li W, Xu J, Xiang Q, Zhuo K, Zhang Y, Liu D Neuroimage Clin. 2022; 34:102970.

PMID: 35240468 PMC: 8889416. DOI: 10.1016/j.nicl.2022.102970.

References

Reid M, White D, Kraguljac N, Lahti A . A combined diffusion tensor imaging and magnetic resonance spectroscopy study of patients with schizophrenia. Schizophr Res. 2016; 170(2-3):341-50. PMC: 5982513. DOI: 10.1016/j.schres.2015.12.003. View

Pomarol-Clotet E, Salvador R, Sarro S, Gomar J, Vila F, Martinez A . Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?. Psychol Med. 2008; 38(8):1185-93. DOI: 10.1017/S0033291708003565. View

Kuhn S, Schubert F, Mekle R, Wenger E, Ittermann B, Lindenberger U . Neurotransmitter changes during interference task in anterior cingulate cortex: evidence from fMRI-guided functional MRS at 3 T. Brain Struct Funct. 2015; 221(5):2541-51. DOI: 10.1007/s00429-015-1057-0. View

Leyba L, Mayer A, Gollub R, Andreasen N, Clark V . Smoking status as a potential confound in the BOLD response of patients with schizophrenia. Schizophr Res. 2008; 104(1-3):79-84. PMC: 2577169. DOI: 10.1016/j.schres.2008.06.008. View

de la Fuente-Sandoval C, Leon-Ortiz P, Favila R, Stephano S, Mamo D, Ramirez-Bermudez J . Higher levels of glutamate in the associative-striatum of subjects with prodromal symptoms of schizophrenia and patients with first-episode psychosis. Neuropsychopharmacology. 2011; 36(9):1781-91. PMC: 3154101. DOI: 10.1038/npp.2011.65. View

Merritt K, Egerton A, Kempton M, Taylor M, McGuire P . Nature of Glutamate Alterations in Schizophrenia: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies. JAMA Psychiatry. 2016; 73(7):665-74. DOI: 10.1001/jamapsychiatry.2016.0442. View

Kraguljac N, White D, Reid M, Lahti A . Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia. JAMA Psychiatry. 2013; 70(12):1294-302. PMC: 7891898. DOI: 10.1001/jamapsychiatry.2013.2437. View

Carter C, Mintun M, Nichols T, Cohen J . Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [15O]H2O PET study during single-trial Stroop task performance. Am J Psychiatry. 1997; 154(12):1670-5. DOI: 10.1176/ajp.154.12.1670. View

Egerton A, Bhachu A, Merritt K, McQueen G, Szulc A, McGuire P . Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A Systematic Review of Longitudinal H-MRS Studies. Front Psychiatry. 2017; 8:66. PMC: 5408014. DOI: 10.3389/fpsyt.2017.00066. View

10.

Lesh T, Niendam T, Minzenberg M, Carter C . Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology. 2010; 36(1):316-38. PMC: 3052853. DOI: 10.1038/npp.2010.156. View

11.

Chiapponi C, Piras F, Piras F, Caltagirone C, Spalletta G . GABA System in Schizophrenia and Mood Disorders: A Mini Review on Third-Generation Imaging Studies. Front Psychiatry. 2016; 7:61. PMC: 4835487. DOI: 10.3389/fpsyt.2016.00061. View

12.

Hepp H, Maier S, Hermle L, Spitzer M . The Stroop effect in schizophrenic patients. Schizophr Res. 1996; 22(3):187-95. DOI: 10.1016/s0920-9964(96)00080-1. View

13.

Shulman R, Hyder F, Rothman D . Insights from neuroenergetics into the interpretation of functional neuroimaging: an alternative empirical model for studying the brain's support of behavior. J Cereb Blood Flow Metab. 2014; 34(11):1721-35. PMC: 4269754. DOI: 10.1038/jcbfm.2014.145. View

14.

Manoach D, Press D, Thangaraj V, Searl M, Goff D, Halpern E . Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry. 1999; 45(9):1128-37. DOI: 10.1016/s0006-3223(98)00318-7. View

15.

Logothetis N . What we can do and what we cannot do with fMRI. Nature. 2008; 453(7197):869-78. DOI: 10.1038/nature06976. View

16.

Friston K, Frith C . Schizophrenia: a disconnection syndrome?. Clin Neurosci. 1995; 3(2):89-97. View

17.

Henik A, Salo R . Schizophrenia and the stroop effect. Behav Cogn Neurosci Rev. 2004; 3(1):42-59. DOI: 10.1177/1534582304263252. View

18.

Hadley J, Nenert R, Kraguljac N, Bolding M, White D, Skidmore F . Ventral tegmental area/midbrain functional connectivity and response to antipsychotic medication in schizophrenia. Neuropsychopharmacology. 2013; 39(4):1020-30. PMC: 3924537. DOI: 10.1038/npp.2013.305. View

19.

Hu M, Zong X, Mann J, Zheng J, Liao Y, Li Z . A Review of the Functional and Anatomical Default Mode Network in Schizophrenia. Neurosci Bull. 2016; 33(1):73-84. PMC: 5567552. DOI: 10.1007/s12264-016-0090-1. View

20.

Kraguljac N, White D, Hadley J, Reid M, Lahti A . Hippocampal-parietal dysconnectivity and glutamate abnormalities in unmedicated patients with schizophrenia. Hippocampus. 2014; 24(12):1524-32. PMC: 7891897. DOI: 10.1002/hipo.22332. View