{"doi":"10.1016/j.brs.2022.07.049","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","abstract":"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.","journal":"Brain stimulation","year":2022,"id":241839,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240151,"name":"Oula Puonti","orcid":"0000-0003-3186-244X","position":1,"is_corresponding":false},{"id":664550,"name":"William T. Clarke","orcid":"0000-0001-7159-7025","position":2,"is_corresponding":false},{"id":871375,"name":"Caroline Nettekoven","orcid":"0000-0001-5427-2907","position":3,"is_corresponding":false},{"id":563591,"name":"Helen C. Barron","orcid":"0000-0002-4575-6472","position":4,"is_corresponding":false},{"id":871376,"name":"James Kolasinski","orcid":"0000-0002-1599-6440","position":5,"is_corresponding":false},{"id":871377,"name":"Taylor Hanayik","orcid":"0000-0003-0751-9844","position":6,"is_corresponding":false},{"id":871378,"name":"Emily L. Hinson","orcid":"0000-0001-6990-4540","position":7,"is_corresponding":false},{"id":458987,"name":"Adam Berrington","orcid":"0000-0002-1207-8193","position":8,"is_corresponding":false},{"id":871379,"name":"Velicia Bachtiar","orcid":"0000-0002-6420-0971","position":9,"is_corresponding":false},{"id":871380,"name":"Ainslie Johnstone","orcid":"0000-0001-9564-6290","position":10,"is_corresponding":false},{"id":109339,"name":"Anderson M. Winkler","orcid":"0000-0002-4169-9781","position":11,"is_corresponding":false},{"id":240155,"name":"Axel Thielscher","orcid":"0000-0002-4752-5854","position":12,"is_corresponding":false},{"id":64975,"name":"Heidi Johansen‐Berg","orcid":"0000-0002-4134-9730","position":13,"is_corresponding":false},{"id":268080,"name":"Charlotte J. Stagg","orcid":"0000-0002-5542-5036","position":14,"is_corresponding":false},{"id":660573,"name":"Tulika Nandi","orcid":"0000-0001-8161-3770","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:00.865267Z","pmid":"35988862","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}