Unveiling Glutamate Dynamics: Cognitive Demands in Human Short-Term Memory Learning Across Frontal and Parieto-Occipital Cortex: A Functional MRS Study.

Background: Acquiring new knowledge necessitates alterations at the synaptic level within the brain. Glutamate, a pivotal neurotransmitter, plays a critical role in these processes, particularly in learning and memory formation. Although previous research has explored glutamate’s involvement in cognitive functions, a comprehensive understanding of its real-time dynamics remains elusive during memory tasks. Objective: This study aimed to investigate glutamate modulation during memory tasks in the right Dorsolateral Prefrontal Cortex (DLPFC) and parieto-occipital regions using functional Magnetic Resonance Spectroscopy (fMRS). Material and Methods: This experimental research applied fMRS acquisition concurrently with a modified Sternberg’s verbal working memory task for fourteen healthy right-handed participants (5 females, mean age=30.64±4.49). The glutamate/total-creatine (Glu/tCr) ratio was quantified by LCModel in the DLPFC and parieto-occipital voxels while applying the tissue corrections. Results: The significantly higher Glu/tCr modulation was observed during the task with a trend of increased modulation with memory load in both the DLPFC (19.9% higher, P-value=0.018) and parieto-occipital (33% higher, P-value=0.046) regions compared to the rest. Conclusion: Our pioneering fMRS study has yielded groundbreaking insights into brain functions during S-term Memory (STM) and learning. This research provides valuable methodological advancements for investigating the metabolic functions of both healthy and disordered brains. Based on the findings, cognitive demands directly correlate with glutamate levels, highlighting the neurochemical underpinnings of cognitive processing. Additionally, the obtained results potentially challenge the traditional left-hemisphere-centric model of verbal working memory, leading to the deep vision of hemispheric contributions to cognitive functions.