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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01260

Influence of Repetitive Transcranial Magnetic Stimulation on Human Neurochemistry and Functional Connectivity: a Pilot MRI/MRS Study at 7 T

  • 1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, United States
  • 2Diagnostic Imaging Center, Kuopio University Hospital, Finland
  • 3Department of Rehabilitation Medicine, University of Minnesota Medical School, United States
  • 4High Field MR Centre, University Clinic for Radiology and Nuclear Medicine, Medical University of Vienna, Austria
  • 5Centro Fermi - Museo storico della fisica e Centro studi e ricerche Enrico Fermi, Italy
  • 6Department of Neurology, University of Minnesota, United States
  • 7University of Minnesota Twin Cities, United States

Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation method commonly used in the disciplines of neuroscience, neurology and neuropsychiatry to examine or modulate brain function. Low frequency rTMS (e.g., 1 Hz) is associated with a net suppression of cortical excitability, whereas higher frequencies (e.g., 5 Hz) purportedly increase excitability. Magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rsfMRI) allow investigation of neurochemistry and functional connectivity, respectively, and can assess the influence of rTMS in these domains. This pilot study investigated the effects of rTMS on the primary motor cortex using pre and post MRS and rsfMRI assessments at 7 T.
Seven right-handed males (age 27±7 y.o.) underwent single-voxel MRS and rsfMRI before and about 30-min after rTMS was administered outside the scanner for 20-min over the primary motor cortex of the left (dominant) hemisphere. All participants received 1-Hz rTMS; one participant additionally received 5-Hz rTMS in a separate session. Concentrations of 17 neurochemicals were quantified in left and right motor cortices. Connectivity metrics included fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) of both motor cortices, strength of related brain networks, and inter-hemispheric connectivity.
The group‐analysis revealed few trends (i.e., uncorrected for multiple comparisons), including a mean increase in the concentration of the inhibitory neurotransmitter -aminobutyric acid (GABA) after the inhibitory rTMS protocol as compared to baseline in the stimulated (left) motor cortex (+8%, p=0.043), along with a slight increase of total creatine (+2%, p=0.018) and decrease of aspartate (-18%, p=0.016). Additionally, GABA tended to decrease in the contralateral hemisphere (-6%, p=0.033). No other changes of metabolite concentrations were found. Whereas functional connectivity outcomes did not exhibit trends of significant changes induced by rTMS, the percent changes of few connectivity metrics in both hemispheres were negatively correlated with GABA changes in the contralateral hemisphere.
While studies in larger cohorts are needed to confirm these preliminary findings, our results indicate the safety and feasibility of detecting changes in key metabolites associated with neurotransmission after a single of 1-Hz rTMS session, establishing the construct for future exploration of the neurochemical and connectivity mechanisms of cortical responses to neuromodulation.

Keywords: GABA, rTMS, MRS, RsfMRI, 7 Tesla, Motor Cortex, inhibition, non-invasive brain stimulation, functional connectivity

Received: 05 Jun 2019; Accepted: 06 Nov 2019.

Copyright: © 2019 Grohn, Gillick, Tkac, Bednarik, Mascali, Deelchand, Michaeli, Meekins, Leffler-McCabe, MacKinnon, Eberly and Mangia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Silvia Mangia, Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, 55455, Minnesota, United States,