A preliminary study of dynamic neurochemical changes in the dorsolateral prefrontal cortex during working memory

• Published in: The European journal of neuroscience 2024-04, Vol.59 (8), p.2075-2086
• Main Authors: Oh, Hyerin, Berrington, Adam, Auer, Dorothee P., Babourina‐Brooks, Ben, Faas, Henryk, Jung, Je Young
• Format: Article
• Language: English
• Subjects: Blood levels; Cognitive ability; DLPFC; fMRI; Functional magnetic resonance imaging; functional magnetic resonance spectroscopy; GABA; glutamate; Glutamatergic transmission; Magnetic resonance imaging; Magnetic resonance spectroscopy; Memory; Neuroimaging; Prefrontal cortex; Spectrum analysis; working memory; γ-Aminobutyric acid
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.16280

Working memory (WM) is one of the fundamental cognitive functions associated with the dorsolateral prefrontal cortex (DLPFC). However, the neurochemical mechanisms of WM, including the dynamic changes in neurometabolites such as glutamate and GABA in the DLPFC, remain unclear. Here, we investigated WM‐related glutamate and GABA changes, alongside hemodynamic responses in the DLPFC, using a combination of functional magnetic resonance spectroscopy (fMRS) and functional magnetic resonance imaging (fMRI). During a WM task, we measured Glx (glutamate + glutamine) and GABA levels using GABA editing MEscher‐GArwood Point REsolved Spectroscopy (MEGA‐PRESS) sequence and blood‐oxygen‐level‐dependent (BOLD) signal changes. In the DLPFC, we observed elevated Glx levels and increased BOLD signal changes during a 2‐back task. Specifically, the Glx levels in the DLPFC were significantly higher during the 2‐back task compared with fixation, although this difference was not significant when compared with a 0‐back task. However, Glx levels during the 0‐back task were higher than during fixation. Furthermore, there was a positive correlation between Glx levels in the DLPFC during the 2‐back task and the corresponding BOLD signal changes. Notably, higher Glx increases were associated with increased DLPFC activation and lower WM task performance in individuals. No notable changes in DLPFC GABA levels were observed during WM processing. These findings suggest that the modulation of glutamatergic activity in the DLPFC may play a crucial role in both working memory processing and its associated performance outcomes. Functional magnetic resonance spectroscopy and functional magnetic resonance imaging were used to examine neurochemical and BOLD signal changes in the dorsolateral prefrontal cortex (DLPFC) during working memory processing. Working memory processing increased the Glx (glutamate + glutamine) levels as well as BOLD signal changes in the DLPFC. Those task‐related changes in Glx levels and BOLD responses were strongly and positively correlated and associated with working memory performance.