{"doi":"10.1038/s41398-021-01264-3","title":"In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial","abstract":"Abstract Recent clinical trials of transcranial direct current stimulation (tDCS) in depression have shown contrasting results. Consequently, we used in-vivo neuroimaging to confirm targeting and modulation of depression-relevant neural circuitry by tDCS. Depressed participants ( N = 66, Baseline Hamilton Depression Rating Scale (HDRS) 17-item scores ≥14 and <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’s 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’s area (BA) 46: p HD = 0.048, Cohen’s d HD = 0.73; p Conv = 0.018, d Conv = 0.86; BA 9: p HD = 0.011, d HD = 0.92; p Conv = 0.022, d Conv = 0.83). Significant longitudinal CBF increases were observed (a) at the left DLPFC stimulation-target for both active montages ( p HD = 3.5E−3, d HD = 0.98; p Conv = 2.8E−3, d Conv = 1.08), and (b) at ACC for the HD-montage only ( p HD = 2.4E−3, d HD = 1.06; p Conv = 0.075, d Conv = 0.64). 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.","journal":"Translational Psychiatry","year":2021,"id":171470,"datarank":0.4943755299006494,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.0,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":706170,"name":"Elizabeth Kim","orcid":"0000-0002-4823-9163","position":1,"is_corresponding":false},{"id":289578,"name":"Cole Anderson","orcid":"0000-0002-4366-6166","position":2,"is_corresponding":false},{"id":314805,"name":"Antoni Kubicki","orcid":"0000-0001-6310-9415","position":3,"is_corresponding":false},{"id":706171,"name":"Rishikesh Kayathi","orcid":"0000-0002-0314-7265","position":4,"is_corresponding":false},{"id":288640,"name":"Kay Jann","orcid":"0000-0003-3574-0538","position":5,"is_corresponding":false},{"id":290779,"name":"Lirong Yan","orcid":"0000-0002-5173-7059","position":6,"is_corresponding":false},{"id":314803,"name":"Amber M. Leaver","orcid":"0000-0002-1518-0708","position":7,"is_corresponding":false},{"id":263474,"name":"Gerhard Hellemann","orcid":"0000-0003-2449-7704","position":8,"is_corresponding":false},{"id":706172,"name":"Marco Iacoboni","orcid":"0000-0002-0035-5413","position":9,"is_corresponding":false},{"id":314807,"name":"Roger P. Woods","orcid":"0000-0001-9679-9571","position":10,"is_corresponding":false},{"id":244996,"name":"Danny J.J. Wang","orcid":"0000-0002-0840-7062","position":11,"is_corresponding":false},{"id":314811,"name":"Katherine L. Narr","orcid":"0000-0002-9396-7936","position":12,"is_corresponding":false},{"id":412110,"name":"Mayank Jog","orcid":"0000-0003-2519-1192","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:46:33.067299Z","pmid":"33627624","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":[]}