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
N1 - Publisher Copyright:
© Copyright © 2019 Gröhn, Gillick, Tkáč, Bednařík, Mascali, Deelchand, Michaeli, Meekins, Leffler-McCabe, MacKinnon, Eberly and Mangia.
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 - GABA
KW - functional connectivity
KW - inhibition
KW - magnetic resonance spectroscopy
KW - motor cortex
KW - non-invasive brain stimulation
KW - repetitive transcranial magnetic stimulation
KW - resting-state functional MRI
UR - http://www.scopus.com/inward/record.url?scp=85076716332&partnerID=8YFLogxK
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U2 - 10.3389/fnins.2019.01260
DO - 10.3389/fnins.2019.01260
M3 - Article
C2 - 31827419
AN - SCOPUS:85076716332
SN - 1662-4548
VL - 13
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 1260
ER -