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

Research output: Contribution to journalArticle

Abstract

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
Volume13
DOIs
StatePublished - Nov 27 2019

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Neurochemistry
Transcranial Magnetic Stimulation
Magnetic Resonance Spectroscopy
Motor Cortex
gamma-Aminobutyric Acid
Magnetic Resonance Imaging
Brain
Neuropsychiatry
Aminobutyrates
Creatine
Neurology
Neurosciences
Aspartic Acid
Synaptic Transmission
Neurotransmitter Agents

Keywords

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

PubMed: MeSH publication types

  • Journal Article

Cite this

@article{7f418c42da554663a1b0a92a1e2677f2,
title = "Influence of Repetitive Transcranial Magnetic Stimulation on Human Neurochemistry and Functional Connectivity: A Pilot MRI/MRS Study at 7 T",
abstract = "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.",
keywords = "functional connectivity, GABA, inhibition, magnetic resonance spectroscopy, motor cortex, non-invasive brain stimulation, repetitive transcranial magnetic stimulation, resting-state functional MRI",
author = "Heidi Gr{\"o}hn and Gillick, {Bernadette T.} and Ivan Tk{\'a}č and Petr Bednař{\'i}k and Daniele Mascali and Deelchand, {Dinesh K.} and Shalom Michaeli and Meekins, {Gregg D.} and Leffler-McCabe, {Michael J.} and MacKinnon, {Colum D.} and Eberly, {Lynn E.} and Silvia Mangia",
year = "2019",
month = "11",
day = "27",
doi = "10.3389/fnins.2019.01260",
language = "English (US)",
volume = "13",
journal = "Frontiers in Neuroscience",
issn = "1662-4548",
publisher = "Frontiers Research Foundation",

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TY - JOUR

T1 - Influence of Repetitive Transcranial Magnetic Stimulation on Human Neurochemistry and Functional Connectivity

T2 - A Pilot MRI/MRS Study at 7 T

AU - Gröhn, Heidi

AU - Gillick, Bernadette T.

AU - Tkáč, Ivan

AU - Bednařík, Petr

AU - Mascali, Daniele

AU - Deelchand, Dinesh K.

AU - Michaeli, Shalom

AU - Meekins, Gregg D.

AU - Leffler-McCabe, Michael J.

AU - MacKinnon, Colum D.

AU - Eberly, Lynn E.

AU - Mangia, Silvia

PY - 2019/11/27

Y1 - 2019/11/27

N2 - 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.

AB - 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.

KW - functional connectivity

KW - GABA

KW - inhibition

KW - magnetic resonance spectroscopy

KW - motor cortex

KW - non-invasive brain stimulation

KW - repetitive transcranial magnetic stimulation

KW - resting-state functional MRI

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