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The in-depth mechanistic understanding of this bipolar and non-focal stimulation technique is still incomplete. In a pilot study, we investigated the effects of bifrontal stimulation on brain metabolite levels and resting state connectivity under the cathode using multiparametric MRI techniques and computational tDCS modeling. Within a double-blind cross-over design, 20 subjects (12 women, 23.7\u2009\u00b1\u20092\u00a0years) were randomized to active tDCS with standard bifrontal montage with the anode over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the right DLPFC. Magnetic resonance spectroscopy (MRS) was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu\u2009+\u2009glutamine (Glx) and gamma aminobutyric acid (GABA) concentration in these areas. Resting-state functional connectivity MRI (rsfcMRI) was acquired before and after the stimulation. The individual distribution of tDCS induced electric fields (efields) within the MRS voxel was computationally modelled using SimNIBS 2.0. There were no significant changes of Glu, Glx and GABA levels across conditions but marked differences in the course of Glu levels between female and male participants\u00a0were observed. Further investigation yielded a significantly stronger Glu reduction after active compared to sham stimulation\u00a0in female participants, but not in male participants. For rsfcMRI neither significant changes nor correlations with MRS data were observed. Exploratory analyses of the effect of efield intensity distribution on Glu changes showed distinct effects in different efield groups. Our findings are limited by the small sample size, but correspond to previously published results of cathodal tDCS. Future studies should address gender and efield intensity as moderators of tDCS induced effects.<\/jats:p>","DOI":"10.1007\/s00406-020-01177-0","type":"journal-article","created":{"date-parts":[[2020,8,2]],"date-time":"2020-08-02T13:02:12Z","timestamp":1596373332000},"page":"111-122","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effects of bifrontal transcranial direct current stimulation on brain glutamate levels and resting state connectivity: multimodal MRI data for the cathodal stimulation site"],"prefix":"10.1007","volume":"271","author":[{"given":"Eva","family":"Mezger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris-Stephan","family":"Rauchmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre R.","family":"Brunoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Bulubas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Thielscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Werle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matin","family":"Mortazavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temmuz","family":"Karali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"St\u00f6cklein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Ertl-Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Goerigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Padberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0244-1024","authenticated-orcid":false,"given":"Daniel","family":"Keeser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,2]]},"reference":[{"key":"1177_CR1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1586\/17434440.2014.911082","volume":"2015","author":"AR Brunoni","year":"2015","unstructured":"Brunoni AR, Shiozawa P, Truong D, Javitt DC (2015) Understanding tDCS effects in schizophrenia : a systematic review of clinical data and an integrated computation modeling analysis Understanding tDCS effects in schizophrenia : a systematic review of clinical data and an integrated computation modeling analysis. 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ARB is sponsored by the Brazilian National Scientific Fund (CNPq-1B) and the Academic Productivity Program (PIPA-A) from the Faculdade de Medicina da UNiversidade de S\u00e3o Paulo. ARB is also medical advisor of Flow Neuroscience and has a small equity of Flow. The work of L.B. is part of a PhD\/residency program of the Ludwig-Maximilians University (LMU) and the International Max Planck Research School for Translational Psychiatry (IMPRS-TP) financially supported by the Else Kr\u00f6ner Fresenius Foundation. AT was supported by the Lundbeck foundation (Grant no. R244-2017-196), and the Novo Nordisk foundation (Grant no. NNF14OC0011413). FP is a member of the European Scientific Advisory Board of Brainsway Inc., Jerusalem, Israel, and has received speaker\u2019s honoraria from Mag&More GmbH and the neuroCare Group. His lab has received support with equipment from neuroConn GmbH, Ilmenau, Germany, and Mag&More GmbH and Brainsway Inc., Jerusalem, Israel. This work was also supported by the German Center for Brain Stimulation (GCBS) research consortium (Work Package 5) [Grant no. 01EE1403E], funded by the Federal Ministry of Education and Research (BMBF).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}