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Longitudinal evaluation of neurochemical modulation induced by quadripulse stimulation (QPS) using ultra-short TE STEAM MRS1Preparing Section for New Faculty of Medical Science, Fukushima Medical University, Fukushima, Japan, 2Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan, 3Department of Neurology, Fukushima Medical University, Fukushima, Japan, 4Department of Radiology, The University of Tokushima Graduate School, Tokushima, Japan
Synopsis
To evaluate longitudinal neurochemical modulation induced by rTMS, we used ultra-short TE STEAM MRS. Glx, GABA and 15 other metabolites were measured using 3T MR equipment longitudinally and LCModel was used to calculate these concentrations quantitatively. QPS was employed as rTMS and left M1 was stimulated in each subject. Five healthy male volunteers participated in this study. The long-term depression intervention induced Glx increment, and the long-term potentiation intervention induced GABA decrement. The present results suggested a usefulness of the ultra-short TE STEAM MRS in evaluation of the longitudinal neurochemical modulation induced by rTMS.
Introduction
Repetitive transcranial magnetic stimulation (rTMS) has emerged to induce lasting synaptic plasticity in the brain. It is able to induce both long-term potentiation (LTP) and long-term depression (LTD) using low-frequency and high-frequency rTMS, respectively. Quadripulse transcranial magnetic stimulation (QPS) is one of the rTMS protocols and is able to induce powerful long term effects constantly. (1) Magnetic resonance spectroscopy (MRS) allows measurements of neurotransmitter concentrations noninvasively in the human brain. The relationship between brain plasticity and neurochemical modulation could be studied by combination of rTMS and MRS. (2-4) Most of reports compared the neurochemical state between before and just after rTMS, but few papers studied longitudinal changes after TMS intervention. The aim of this study was to evaluate the longitudinal neurochemical modulation induced by QPS using ultra-short TE STEAM MRS.Materials and Methods
Five healthy male volunteers (age=24.6 ± 5.8 y.o.) participated in this study. The institutional review boards approved the study and informed consent was obtained from all of the participants. Biograph mMR (Siemens Healthcare) with 12 channel head coil was used. Task functional MRI with finger tapping/rest in block design was performed to identify primary motor cortex hand area (M1) prior to the experiment. QPS with short interval (QPS5ms.) and long interval (QPS50ms.) over left M1 were employed to induce LTP and LTD in M1, respectively. Single voxel stimulated echo acquisition mode (STEAM) sequence with TR=3000ms. and TE=6ms. was used to measure metabolites in both the stimulated and contralateral sites. VOI volume was 8cm3. LCModel software was used to calculate concentrations of the metabolites quantitatively. Longitudinal changes in the concentration of glutamate and glutamine complex (Glx), gamma-aminobutyric acid (GABA), and 15 other metabolites were evaluated before and after the interventions up to 65min. Each metabolite concentration was normalized by the concentration of total creatine at each time point. The longitudinal changes in the corticospinal excitability was evaluated by motor evoked potentials (MEP) size after intervention. All measurement data were normalized by the data obtained before the intervention. On a day apart from the QPS experiments by at least a week, neurophysiological assessments were performed in all the subjects.Results
Normalized Glx concentrations at 65min after QPS50ms intervention were greater than those by QPS5ms at stimulated site. There were no specific differences between QPS5ms and QPS50ms interventions at contralateral site. (fig.1) Normalized GABA concentrations after QPS5ms intervention were significantly lower than those by QPS50ms at the stimulated site. (fig. 2) The normalized MEP size negatively correlated with the normalized GABA concentration. (fig. 3)Disscussion
We investigated longitudinal changes in the neurotransmitters induced by QPS using ultra-short TE STEAM MRS. Our result of Glx concentration increment after LTD induction was consistent with a previous report. (2) The QPS5ms intervention (LTP induction) significantly reduced GABA concentration at the stimulated site for 60min. This finding was also comparable with a previous report of continuous theta burst stimulation (cTBS). (4) A negative correlation between normalized MEP size and normalized GABA concentration suggested that GABAergic inhibition may partly cause MEP size changes after QPS. We showed long term neurotransmitter changes after non-invasive brain stimulation methods in the human brain.Conclusion
Ultra-short TE STEAM sequence is useful for evaluating longitudinal neurochemical modulation induced by rTMS.Acknowledgements
The STEAM sequence was provided by the Center for Magnetic Resonance Research, University of Minnesota.References
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