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

Abstract

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. © The Author(s), under exclusive licence to Marta Olivetti Belardinelli 2025.