Dynamics of Glutamate and Glutamine Assessed Using MRS in Response to a Short Heat Pain Stimulation

It is assumed that the mechanism of changes in neurotransmitter levels measured by MRS in the short period of response to stimulation differs from the long one. According to compartmental shift hypothesis, the rapid increase in the MRS-measured level of neurotransmitters after event-related stimulus is due to their release from vesicles, and the subsequent decrease is due to their refilling. To test this hypothesis, we studied the concentration of the sum of glutamate and glutamine (Glx) in response to a short painful thermal stimulus. fMRI data and PRESS magnetic resonance spectra [echo time/repetition time = 35 ms/2000 ms] of an activated area in the left insular cortex of 26 subjects were acquired using a 3-T MR scanner. Stimulation was performed by presenting painful heat stimulus for 3 s, repeated with an interval of 7-9 s. The time course of Glx, N-acetylaspartate (NAA), and creatine (Cr) concentrations and the width and height of resonance lines were obtained with a nominal time resolution of 2 s. Changes in the linewidth and height of N-acetylaspartate and Cr signals were used to determine the BOLD effect. Seven subjects were excluded from analyses due to bad spectral quality or high Glx change in the dynamics. Because of nonreliable stimulation, analysis of response to stimulation was conducted in the two groups (less and more activated). In response to the activation, the Glx as the Glx/Cr ratio maximal increases were 4.2% ± 1.4% and 5.2% ± 1.4% (p < 0.05), respectively in 2 s after the establishing the stimulus temperature. Time courses of Cr and NAA signal width and height showed statistically significant decrease of Cr at 4 s after stimulus onset (-2.6% ± 0.8%, p = 0.03). The sensitivity of MRS to the BOLD effect was lower than that of the fMRI method. In the short response period, a short-term increase in the Glx level is observed. This result is in line with the compartmental shift hypothesis for short-term neurotransmitter dynamics, but further work is necessary to directly confirm this interpretation. Reliable detection of rapid increases in neurotransmitter levels following a short stimulus requires robust neural activation and minimal motion-related artifacts.