Increased Glutamate concentrations during prolonged motor activation as measured using functional Magnetic Resonance Spectroscopy at 3T

Abstract

Recent implications of glutamatergic signaling in a wide range of psychiatric disorders has highlighted the need to study the dynamics of glutamate (Glu) in the brain outside of steady state. A promising modality for doing so is functional Magnetic Resonance Spectroscopy (fMRS). Recent human studies at high magnetic fields (7T) have reported small but consistent changes in metabolite concentrations, in particular a 2–4% increase in Glu during visual and motor stimulation. While the origins of these changes remain the topic of ongoing research, the ability of fMRS to observe metabolites directly associated with neurotransmission and brain energetics could potentially aid our understanding of brain pathophysiology and the interpretation of functional imaging experiments. For this to happen, the current ultrahigh field results must be reproduced at lower, widely available clinical field strengths, in response to a wide variety of stimuli classes. Our goal herein was to investigate metabolite changes during a hand-clenching motor task at 3T, and to investigate the effect of the stimulation's temporal characteristics on the magnitude of the fMRS changes; specifically, we compared two block-designed functional activation paradigms, using short- and long-cycled clenching designs. Small but statistically significant increases in Glx=Glutamate+Glutamine (3.8%) and Glu (4.0%) concentrations were detected during the long-cycled design, while no statistically significant changes were observed during the short-cycled design. Activation during the long-cycled tasks was correlated to the frequency of clenching. We have also shown that using subject-level analysis in combination with a linear mixed model increases the observed effect size, and could help analyzing the weak MRS signals. Our results are in good agreement with the previous reports acquired at higher field systems, and support the viability of fMRS as a research tool at clinical field strengths, while also emphasizing the importance of the functional paradigm itself.