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tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Nandi, Tulika; Puonti, Oula; Clarke, William T; Nettekoven, Caroline; Barron, Helen C; Kolasinski, James; Hanayik, Taylor; Hinson, Emily L; Berrington, Adam; Bachtiar, Velicia; Johnstone, Ainslie; Winkler, Anderson M; Thielscher, Axel; Johansen-Berg, Heidi; Stagg, Charlotte J


Tulika Nandi

Oula Puonti

William T Clarke

Caroline Nettekoven

Helen C Barron

James Kolasinski

Taylor Hanayik

Emily L Hinson

Velicia Bachtiar

Ainslie Johnstone

Anderson M Winkler

Axel Thielscher

Heidi Johansen-Berg

Charlotte J Stagg


BACKGROUND AND OBJECTIVE: Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. METHODS: Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N=24) or right temporal cortex (2 studies, N=32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. RESULTS: In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24)=3.24, p=0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24)=-3.55, p=0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. CONCLUSIONS: Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects.


Nandi, T., Puonti, O., Clarke, W. T., Nettekoven, C., Barron, H. C., Kolasinski, J., …Stagg, C. J. (2022). tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel. Brain Stimulation, 15(5), 1153-1162.

Journal Article Type Article
Acceptance Date Jul 26, 2022
Online Publication Date Aug 18, 2022
Publication Date Sep 1, 2022
Deposit Date Sep 13, 2022
Publicly Available Date Sep 13, 2022
Journal Brain stimulation
Print ISSN 1935-861X
Electronic ISSN 1876-4754
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 15
Issue 5
Pages 1153-1162
Keywords Neurology (clinical); Biophysics; General Neuroscience
Public URL
Publisher URL


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