tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel
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,...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Brain Stimulation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X22001681 |
| _version_ | 1811182535703527424 |
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| author | Tulika Nandi Oula Puonti William T. Clarke Caroline Nettekoven Helen C. Barron James Kolasinski Taylor Hanayik Emily L. Hinson Adam Berrington Velicia Bachtiar Ainslie Johnstone Anderson M. Winkler Axel Thielscher Heidi Johansen-Berg Charlotte J. Stagg |
| author_facet | Tulika Nandi Oula Puonti William T. Clarke Caroline Nettekoven Helen C. Barron James Kolasinski Taylor Hanayik Emily L. Hinson Adam Berrington Velicia Bachtiar Ainslie Johnstone Anderson M. Winkler Axel Thielscher Heidi Johansen-Berg Charlotte J. Stagg |
| author_sort | Tulika Nandi |
| collection | DOAJ |
| description | 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 1 mA 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. |
| first_indexed | 2024-04-11T09:32:13Z |
| format | Article |
| id | doaj.art-5d725bf458fd4147a1eaaab59b20de9e |
| institution | Directory Open Access Journal |
| issn | 1935-861X |
| language | English |
| last_indexed | 2024-04-11T09:32:13Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj.art-5d725bf458fd4147a1eaaab59b20de9e2022-12-22T04:31:49ZengElsevierBrain Stimulation1935-861X2022-09-0115511531162tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxelTulika Nandi0Oula Puonti1William T. Clarke2Caroline Nettekoven3Helen C. Barron4James Kolasinski5Taylor Hanayik6Emily L. Hinson7Adam Berrington8Velicia Bachtiar9Ainslie Johnstone10Anderson M. Winkler11Axel Thielscher12Heidi Johansen-Berg13Charlotte J. Stagg14Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; NeuroImaging Center (NIC), Johannes Gutenberg University Medical Center, Germany; Corresponding author. FMRIB Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU UK.Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, DenmarkWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UKWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UKWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, UKCUBRIC, Cardiff University, UKWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UKWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UKSir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, UKWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UKUniversity College London, UKNational Institute of Mental Health, National Institutes of Health, United StatesDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, DenmarkWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UKWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, UKBackground 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 1 mA 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.http://www.sciencedirect.com/science/article/pii/S1935861X22001681electric fieldtDCSModellingGABAInter-individual variabilityMRS |
| spellingShingle | Tulika Nandi Oula Puonti William T. Clarke Caroline Nettekoven Helen C. Barron James Kolasinski Taylor Hanayik Emily L. Hinson Adam Berrington Velicia Bachtiar Ainslie Johnstone Anderson M. Winkler Axel Thielscher Heidi Johansen-Berg Charlotte J. Stagg 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 electric field tDCS Modelling GABA Inter-individual variability MRS |
| title | tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel |
| title_full | tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel |
| title_fullStr | tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel |
| title_full_unstemmed | tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel |
| title_short | tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel |
| title_sort | tdcs induced gaba change is associated with the simulated electric field in m1 an effect mediated by grey matter volume in the mrs voxel |
| topic | electric field tDCS Modelling GABA Inter-individual variability MRS |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X22001681 |
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