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Consequently, we used in-vivo neuroimaging to confirm targeting and modulation of depression-relevant neural circuitry by tDCS. Depressed participants (<jats:italic>N<\/jats:italic>\u2009=\u200966, Baseline Hamilton Depression Rating Scale (HDRS) 17-item scores \u226514 and &lt;24) were randomized into Active\/Sham and High-definition (HD)\/Conventional (Conv) tDCS groups using a double-blind, parallel design, and received tDCS individually targeted at the left dorsolateral prefrontal cortex (DLPFC). In accordance with Ampere\u2019s Law, tDCS currents were hypothesized to induce magnetic fields at the stimulation-target, measured in real-time using dual-echo echo-planar-imaging (DE-EPI) MRI. Additionally, the tDCS treatment trial (consisting of 12 daily 20-min sessions) was hypothesized to induce cerebral blood flow (CBF) changes post-treatment at the DLPFC target and in the reciprocally connected anterior cingulate cortex (ACC), measured using pseudo-continuous arterial spin labeling (pCASL) MRI. Significant tDCS current-induced magnetic fields were observed at the left DLPFC target for both active stimulation montages (Brodmann\u2019s area (BA) 46: <jats:italic>p<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20090.048, Cohen\u2019s <jats:italic>d<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20090.73; <jats:italic>p<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20090.018, <jats:italic>d<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20090.86; BA 9: <jats:italic>p<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20090.011, <jats:italic>d<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20090.92; <jats:italic>p<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20090.022, <jats:italic>d<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20090.83). Significant longitudinal CBF increases were observed (a) at the left DLPFC stimulation-target for both active montages (<jats:italic>p<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20093.5E\u22123, <jats:italic>d<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20090.98; <jats:italic>p<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20092.8E\u22123, <jats:italic>d<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20091.08), and (b) at ACC for the HD-montage only (<jats:italic>p<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20092.4E\u22123, <jats:italic>d<\/jats:italic><jats:sub>HD<\/jats:sub>\u2009=\u20091.06; <jats:italic>p<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20090.075, <jats:italic>d<\/jats:italic><jats:sub>Conv<\/jats:sub>\u2009=\u20090.64). These results confirm that tDCS-treatment (a) engages the stimulation-target, and (b) modulates depression-relevant neural circuitry in depressed participants, with stronger network-modulations induced by the HD-montage. Although not primary outcomes, active HD-tDCS showed significant improvements of anhedonia relative to sham, though HDRS scores did not differ significantly between montages post-treatment.<\/jats:p>","DOI":"10.1038\/s41398-021-01264-3","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T14:18:43Z","timestamp":1614176323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-1192","authenticated-orcid":false,"given":"Mayank. 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