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

Heidi Gröhn, Bernadette T. Gillick, Ivan Tkáč, Petr Bednařík, Daniele Mascali, Dinesh K. Deelchand, Shalom Michaeli, Gregg D. Meekins, Michael J. Leffler-McCabe, Colum D. MacKinnon, Lynn E. Eberly, Silvia Mangia

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4 Scopus citations


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 γ-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 1-Hz rTMS session, establishing the construct for future exploration of the neurochemical, and connectivity mechanisms of cortical responses to neuromodulation.

Original languageEnglish (US)
Article number1260
JournalFrontiers in Neuroscience
StatePublished - Nov 27 2019

Bibliographical note

Funding Information:
This research was supported by the University of Minnesota (Medical School Innovation Grant), the National Institutes of Health (P41 EB015894, P30 NS076408, and K01 HD078484), and the Instrumentarium Science Foundation, Finland. PB was partially supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (Grant No. 27238) and the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 846793. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding bodies.


  • GABA
  • functional connectivity
  • inhibition
  • magnetic resonance spectroscopy
  • motor cortex
  • non-invasive brain stimulation
  • repetitive transcranial magnetic stimulation
  • resting-state functional MRI

PubMed: MeSH publication types

  • Journal Article

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