Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers

E. Mezger; B.S. Rauchmann; A.R. Brunoni; L. Bulubas; Axel Thielscher; J. Werle; M. Mortazavi; T. Karali; S. Stöcklein; B. Ertl-Wagner; S. Goerigk; F. Padberg; D. Keeser

doi:10.1016/j.clinph.2019.12.310

Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers

E. Mezger, B.S. Rauchmann, A.R. Brunoni, L. Bulubas, Axel Thielscher, J. Werle, M. Mortazavi, T. Karali, S. Stöcklein, B. Ertl-Wagner, S. Goerigk, F. Padberg, D. Keeser

Research output: Contribution to journal › Conference abstract in journal › Research › peer-review

Abstract

Introduction: Transcranial direct current stimulation (tDCS) of prefrontal cortex (PFC) regions is a widely used experimental intervention in neuroscience as well as a novel therapeutic approach in psychiatry. However, its mechanistic understanding is still under investigation. In this conceptual study, we combined online tDCS, MR spectroscopy (MRS), resting state functional MRI connectivity (rsfcMRI) and computational modeling of tDCS induced electric fields in order to investigate the effect of prefrontal tDCS on brain metabolites and resting-state functional connectivity in relation to the respective modeled efield. Methods: In a double-blind cross-over design, 19 subjects (11 women, mean age 23) underwent both active and sham tDCS (anode – F3, cathode – F4) in randomized sequential order. MRS was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma-aminobutyric acid (GABA) concentration. RsfcMRI measurements were run before and after the stimulation. Additionally, efield distribution was modelled to explore relations between efield, rsfcMRI and MRS. Results: A reduction of Glu concentration during active tDCS was observed in the investigated area of the right dorsolateral PFC located under the cathode. Significant modulation of network connectivity from this area to the whole brain was observed. Additionally, we found large variations in electrical field distribution
across individuals with varying outreach in the MRS target region. Investigation of gender specific responses showed stronger tDCS effects in women. Conclusion: Glu under the cathode during prefrontal tDCS may partially depend on gender and intensity of the tDCS induced efield. This is in line with a very recently published study (Antonenko et al., 2019). For future studies multivoxel MRS with online tDCS including computational efield modeling could be a promising opportunity for a deeper mechanistic understanding of tDCS induced effects in the human brain.

Original language	English
Journal	Clinical Neurophysiology
Volume	131
Issue number	4
Pages (from-to)	e127
Number of pages	1
ISSN	1388-2457
DOIs	https://doi.org/10.1016/j.clinph.2019.12.310
Publication status	Published - 2020

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Mezger, E., Rauchmann, B. S., Brunoni, A. R., Bulubas, L., Thielscher, A., Werle, J., Mortazavi, M., Karali, T., Stöcklein, S., Ertl-Wagner, B., Goerigk, S., Padberg, F., & Keeser, D. (2020). Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers. Clinical Neurophysiology, 131(4), e127. https://doi.org/10.1016/j.clinph.2019.12.310

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title = "Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers",

abstract = "Introduction: Transcranial direct current stimulation (tDCS) of prefrontal cortex (PFC) regions is a widely used experimental intervention in neuroscience as well as a novel therapeutic approach in psychiatry. However, its mechanistic understanding is still under investigation. In this conceptual study, we combined online tDCS, MR spectroscopy (MRS), resting state functional MRI connectivity (rsfcMRI) and computational modeling of tDCS induced electric fields in order to investigate the effect of prefrontal tDCS on brain metabolites and resting-state functional connectivity in relation to the respective modeled efield. Methods: In a double-blind cross-over design, 19 subjects (11 women, mean age 23) underwent both active and sham tDCS (anode – F3, cathode – F4) in randomized sequential order. MRS was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma-aminobutyric acid (GABA) concentration. RsfcMRI measurements were run before and after the stimulation. Additionally, efield distribution was modelled to explore relations between efield, rsfcMRI and MRS. Results: A reduction of Glu concentration during active tDCS was observed in the investigated area of the right dorsolateral PFC located under the cathode. Significant modulation of network connectivity from this area to the whole brain was observed. Additionally, we found large variations in electrical field distributionacross individuals with varying outreach in the MRS target region. Investigation of gender specific responses showed stronger tDCS effects in women. Conclusion: Glu under the cathode during prefrontal tDCS may partially depend on gender and intensity of the tDCS induced efield. This is in line with a very recently published study (Antonenko et al., 2019). For future studies multivoxel MRS with online tDCS including computational efield modeling could be a promising opportunity for a deeper mechanistic understanding of tDCS induced effects in the human brain. ",

author = "E. Mezger and B.S. Rauchmann and A.R. Brunoni and L. Bulubas and Axel Thielscher and J. Werle and M. Mortazavi and T. Karali and S. St{\"o}cklein and B. Ertl-Wagner and S. Goerigk and F. Padberg and D. Keeser",

year = "2020",

doi = "10.1016/j.clinph.2019.12.310",

language = "English",

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Mezger, E, Rauchmann, BS, Brunoni, AR, Bulubas, L, Thielscher, A, Werle, J, Mortazavi, M, Karali, T, Stöcklein, S, Ertl-Wagner, B, Goerigk, S, Padberg, F & Keeser, D 2020, 'Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers', Clinical Neurophysiology, vol. 131, no. 4, pp. e127. https://doi.org/10.1016/j.clinph.2019.12.310

Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers. / Mezger, E.; Rauchmann, B.S.; Brunoni, A.R. et al.
In: Clinical Neurophysiology, Vol. 131, No. 4, 2020, p. e127.

Research output: Contribution to journal › Conference abstract in journal › Research › peer-review

TY - ABST

T1 - Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers

AU - Mezger, E.

AU - Rauchmann, B.S.

AU - Brunoni, A.R.

AU - Bulubas, L.

AU - Thielscher, Axel

AU - Werle, J.

AU - Mortazavi, M.

AU - Karali, T.

AU - Stöcklein, S.

AU - Ertl-Wagner, B.

AU - Goerigk, S.

AU - Padberg, F.

AU - Keeser, D.

PY - 2020

Y1 - 2020

N2 - Introduction: Transcranial direct current stimulation (tDCS) of prefrontal cortex (PFC) regions is a widely used experimental intervention in neuroscience as well as a novel therapeutic approach in psychiatry. However, its mechanistic understanding is still under investigation. In this conceptual study, we combined online tDCS, MR spectroscopy (MRS), resting state functional MRI connectivity (rsfcMRI) and computational modeling of tDCS induced electric fields in order to investigate the effect of prefrontal tDCS on brain metabolites and resting-state functional connectivity in relation to the respective modeled efield. Methods: In a double-blind cross-over design, 19 subjects (11 women, mean age 23) underwent both active and sham tDCS (anode – F3, cathode – F4) in randomized sequential order. MRS was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma-aminobutyric acid (GABA) concentration. RsfcMRI measurements were run before and after the stimulation. Additionally, efield distribution was modelled to explore relations between efield, rsfcMRI and MRS. Results: A reduction of Glu concentration during active tDCS was observed in the investigated area of the right dorsolateral PFC located under the cathode. Significant modulation of network connectivity from this area to the whole brain was observed. Additionally, we found large variations in electrical field distributionacross individuals with varying outreach in the MRS target region. Investigation of gender specific responses showed stronger tDCS effects in women. Conclusion: Glu under the cathode during prefrontal tDCS may partially depend on gender and intensity of the tDCS induced efield. This is in line with a very recently published study (Antonenko et al., 2019). For future studies multivoxel MRS with online tDCS including computational efield modeling could be a promising opportunity for a deeper mechanistic understanding of tDCS induced effects in the human brain.

AB - Introduction: Transcranial direct current stimulation (tDCS) of prefrontal cortex (PFC) regions is a widely used experimental intervention in neuroscience as well as a novel therapeutic approach in psychiatry. However, its mechanistic understanding is still under investigation. In this conceptual study, we combined online tDCS, MR spectroscopy (MRS), resting state functional MRI connectivity (rsfcMRI) and computational modeling of tDCS induced electric fields in order to investigate the effect of prefrontal tDCS on brain metabolites and resting-state functional connectivity in relation to the respective modeled efield. Methods: In a double-blind cross-over design, 19 subjects (11 women, mean age 23) underwent both active and sham tDCS (anode – F3, cathode – F4) in randomized sequential order. MRS was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma-aminobutyric acid (GABA) concentration. RsfcMRI measurements were run before and after the stimulation. Additionally, efield distribution was modelled to explore relations between efield, rsfcMRI and MRS. Results: A reduction of Glu concentration during active tDCS was observed in the investigated area of the right dorsolateral PFC located under the cathode. Significant modulation of network connectivity from this area to the whole brain was observed. Additionally, we found large variations in electrical field distributionacross individuals with varying outreach in the MRS target region. Investigation of gender specific responses showed stronger tDCS effects in women. Conclusion: Glu under the cathode during prefrontal tDCS may partially depend on gender and intensity of the tDCS induced efield. This is in line with a very recently published study (Antonenko et al., 2019). For future studies multivoxel MRS with online tDCS including computational efield modeling could be a promising opportunity for a deeper mechanistic understanding of tDCS induced effects in the human brain.

U2 - 10.1016/j.clinph.2019.12.310

DO - 10.1016/j.clinph.2019.12.310

M3 - Conference abstract in journal

SN - 1388-2457

VL - 131

SP - e127

JO - Clinical Neurophysiology

JF - Clinical Neurophysiology

IS - 4

ER -

Effects of prefrontal cathodal tDCS on brain glutamate levels and resting state connectivity: A randomized, sham-controlled, cross-over trial in healthy volunteers

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