GABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits

Abstract The perception of a voice in the absence of an external auditory source—an auditory verbal hallucination—is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address t...

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Main Authors: Alexander R. Craven, Gerard Dwyer, Lars Ersland, Katarzyna Kazimierczak, Lin Lilleskare, Ralph Noeske, Lydia Brunvoll Sandøy, Erik Johnsen, Kenneth Hugdahl
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-03644-x
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author Alexander R. Craven
Gerard Dwyer
Lars Ersland
Katarzyna Kazimierczak
Lin Lilleskare
Ralph Noeske
Lydia Brunvoll Sandøy
Erik Johnsen
Kenneth Hugdahl
author_facet Alexander R. Craven
Gerard Dwyer
Lars Ersland
Katarzyna Kazimierczak
Lin Lilleskare
Ralph Noeske
Lydia Brunvoll Sandøy
Erik Johnsen
Kenneth Hugdahl
author_sort Alexander R. Craven
collection DOAJ
description Abstract The perception of a voice in the absence of an external auditory source—an auditory verbal hallucination—is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate + Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task.
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spelling doaj-art-7bf28b6c7b1e48809f7e1b8689a999a62025-08-20T03:10:35ZengNature PortfolioScientific Reports2045-23222025-06-0115111310.1038/s41598-025-03644-xGABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traitsAlexander R. Craven0Gerard Dwyer1Lars Ersland2Katarzyna Kazimierczak3Lin Lilleskare4Ralph Noeske5Lydia Brunvoll Sandøy6Erik Johnsen7Kenneth Hugdahl8Department of Biological and Medical Psychology, University of BergenDepartment of Biological and Medical Psychology, University of BergenDepartment of Clinical Engineering, Haukeland University HospitalInstitute of Computer Science, Czech Academy of SciencesDivision of Psychiatry, Haukeland University HospitalGE HealthCareDepartment of Biological and Medical Psychology, University of BergenDivision of Psychiatry, Haukeland University HospitalDepartment of Biological and Medical Psychology, University of BergenAbstract The perception of a voice in the absence of an external auditory source—an auditory verbal hallucination—is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate + Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task.https://doi.org/10.1038/s41598-025-03644-xGABAGlutamateMEGA-PRESSFunctional spectroscopyHallucinationsPsychosis
spellingShingle Alexander R. Craven
Gerard Dwyer
Lars Ersland
Katarzyna Kazimierczak
Lin Lilleskare
Ralph Noeske
Lydia Brunvoll Sandøy
Erik Johnsen
Kenneth Hugdahl
GABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits
Scientific Reports
GABA
Glutamate
MEGA-PRESS
Functional spectroscopy
Hallucinations
Psychosis
title GABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits
title_full GABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits
title_fullStr GABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits
title_full_unstemmed GABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits
title_short GABA, glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits
title_sort gaba glutamate dynamics and bold observed during cognitive processing in psychosis patients with hallucinatory traits
topic GABA
Glutamate
MEGA-PRESS
Functional spectroscopy
Hallucinations
Psychosis
url https://doi.org/10.1038/s41598-025-03644-x
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