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Human short-term memory learning based on dynamic glutamate levels and oscillatory activities: concurrent metabolic and electrophysiological studies using event-related functional-MRS and EEG modalities

Authors: Mohammadi HZargaran SJKhajehpour HAdibi IRahimiforoushani AKarimi SSerej NDAlam NR


Affiliations

1 Department of Bioimaging, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences (IUMS), Isfahan, Iran.
2 Multimodal Functional Imaging Lab, Department of Physics and PERFORM Centre, Concordia University, Montreal, Quebec, Canada.
3 Department of Neurology, School of Medicine, Isfahan University of Medical Sciences (IUMS), Isfahan, Iran.
4 Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
5 Department of Epidemiology & Biostatistics, School of Public Health, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
6 Department of Medical Physics & Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
7 Department of Bioimaging, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences (IUMS), Isfahan, Iran. nasim.dadashiserej@uwl.ac.uk.
8 School of Computing and Engineering, University of West London, London, W5 5RF, UK. nasim.dadashiserej@uwl.ac.uk.
9 Department of Medical Physics & Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran. riahialam@gmail.com.
10 Magnetic Resonance Imaging Lab, National Brain Mapping Laboratory (NBML), Tehran, Iran. riahialam@gmail.com.

Description

Short-term memory (STM) temporarily stores sensory information, critical for synaptic plasticity, memory, and learning, and is regulated by the glutamate-gated NMDA receptor. While the frontal and parieto-occipital cortices have been implicated in STM, the electrochemical dynamics of the right hemisphere under cognitive loads remain underexplored. Utilizing a novel fMRS-EEG approach, we concurrently investigated the metabolic and electrophysiological dynamics of STM for the first time. Fourteen healthy right-handed participants (mean age = 30.64 ± 4.49; 5 females) engaged in a modified Sternberg task with two, four, and six letters. We quantified Glutamate/total-creatine (Glu/tCr) in the right dorsolateral prefrontal cortex (DLPFC) and parieto-occipital regions using LCModel. Concurrently, EEG oscillatory activities were recorded over these areas, focusing on glutamate levels and related electrical activities. Increased Glu/tCr ratios were noted with higher memory loads in the DLPFC (25%, p = 0.018) and parieto-occipital cortex (29.6%, p = 0.046). Gamma activity rose with glutamate levels (DLPFC: F(3,39) = 5.93, p = 0.005; parieto-occipital: F(3,39) = 9.23, p < 0.001), while alpha power was suppressed in the parieto-occipital region (F(3,39) = 6.22, p = 0.022). Theta oscillations correlated positively with Glu/tCr in the DLPFC (r = 0.317, p = 0.017) and negatively in the parieto-occipital (r = - 0.576, p < 0.001). Our findings reveal a significant interplay between glutamate metabolism and neuronal oscillations during STM, emphasizing the roles of the right DLPFC and parieto-occipital regions, which may inform hypotheses about the mechanisms underlying learning. However, we did not measure consolidation, and causal claims about synaptic plasticity are not warranted.


Keywords: Functional event-related MRS (fMRS)Glutamate levelsMetabolic brain mappingNeurons electrical activityShort-term memory-learningVolume &source localization


Links

PubMed: https://pubmed.ncbi.nlm.nih.gov/41171530/

DOI: 10.1007/s10339-025-01317-1