Depression treatment by tDCS-enhanced cognitive control training: A test of two stimulation intensities

Hypoactivity of the dorsolateral prefrontal cortex (dlPFC) has been described as a pathophysiological characteristic major depression disorder (MDD) [[1]Fales C.L. Barch D.M. Rundle M.M. Mintun M.A. Snyder A.Z. Cohen J.D. et al.Altered emotional interference processing in affective and cognitive-control brain circuitry depression.Biol Psychiatr. 2008; 63: 377-384https://doi.org/10.1016/j.biopsych.2007.06.012Abstract Full Text PDF PubMed Scopus (349) Google Scholar] which is associated with impaired cognitive control over negative information, underlying development maintenance MDD symptomatology [[2]Gotlib I.H. Joormann J. Cognition depression: current status future directions.Annu Rev Clin Psychol. 2010; 6: 285-312https://doi.org/10.1146/annurev.clinpsy.121208.131305Crossref (1261) Scholar]. DlPFC activity can be modulated by transcranial direct stimulation (tDCS) studies on efficacy tDCS for are promising [[3]Razza L.B. Palumbo P. Moffa A.H. Carvalho A.F. Solmi M. Loo C.K. al.A systematic review meta-analysis effects depressive episodes.Depress Anxiety. 2020; 37: 594-608https://doi.org/10.1002/da.23004Crossref (32) However, reported effect sizes moderate knowledge optimal parameters, like intensity still lacking. Since itself does not induce neuronal activity, its depends concurrent activity. Thus, targeted combination training (CCT) put forward approach to support antidepressive [[4]Segrave R.A. Arnold S. Hoy K. Fitzgerald P.B. Concurrent augments antidepressant tDCS: pilot study.Brain Stimul. 2014; 7: 325-331https://doi.org/10.1016/j.brs.2013.12.008Abstract (132) Scholar,[5]Brunoni A.R. Boggio P.S. De Raedt R. Benseñor I.M. Lotufo P.A. Namur V. al.Cognitive therapy randomized, double-blinded, controlled trial.J Affect Disord. 162: 43-49https://doi.org/10.1016/j.jad.2014.03.026Crossref (139) Particularly trainings paced auditory serial addition task [PASAT, [6]Gronwall D. Paced serial-addition task: measure recovery from concussion.Percept Mot Skills. 1977; 44: 367-373https://doi.org/10.2466/pms.1977.44.2.367Crossref (1830) Scholar indicated symptoms [[7]Siegle G.J. Ghinassi F. Thase M.E. Neurobehavioral therapies 21st century: summary an emerging field extended example depression.Cognit Ther Res. 2007; 31: 235-262https://doi.org/10.1007/s10608-006-9118-6Crossref (311) The PASAT challenges information means continuous working memory updating stressful frustrating environment Consistently, performance activates dlPFC [[8]Lazeron R.H. Rombouts S.A.R. de Sonneville L. Barkhof Scheltens A visual test fMRI.J Neurol Sci. 2003; 213: 29-34https://doi.org/10.1016/S0022-510X(03)00144-8Abstract (61) Given this complementary impact CCT network biased processing, synergistic expected. Therefore, we tested supported using two intensities (1 2mA) investigate most effective based previous results healthy subjects showing non-linear influence beneficial 1 but 2 mA [[9]Weller Nitsche Plewnia C. Enhancing stimulation: parameter 13: 1358-1369https://doi.org/10.1016/j.brs.2020.07.006Abstract (7) 51 depressed patients (30 female, M = 37.71 years, SD 14.02) were randomly allocated into one three conditions + sham tDCS, 1mA 2mA (N 3 × 17, Sup. Table 1). Exclusion criteria left-handedness, instable intake medication, anticonvulsants, opiates, excessive benzodiazepine use (>1mg Lorazepam/equivalent dose other Benzodiazepines per day), bipolar disorder, schizophrenia spectrum substance eating Cluster A, antisocial or borderline personality acute suicidality. study was approved local ethics committee conducted compliance Declaration Helsinki. All participants gave their written informed consent. registered at ClinicalTrials.gov (Identifier: NCT03518749). completed four-week training, comprising intermittent sessions week (Monday, Wednesday, Friday). As task, used adaptive version PASAT. One-digit numbers presented via headphones added digit they just heard before. Simultaneously new digit, feedback given presenting green (red) light after correct (incorrect) responses. An inter-stimulus interval (ISI) ensured that processed individual limits overstrained. Starting s it increased (decreased) 0.1 four consecutive incorrect (correct) trials. administered parallel 23 minutes (5 seconds ramp up/down) multichannel DC Stimulator (NeuroConn GmbH, Germany) 35cm2 rubber electrodes placed left (F3 active, anodal electrode) right deltoid muscle (reference, cathodal electrode). In group, terminated 30 seconds. Depressive assessed Montgomery Asberg Depression Rating Scale (MADRS) blinded, trained psychologists seven time points: baseline (BL), weeks1–4, post session three-month follow-up (FU). followed controlled, between-subjects design. experimenter blinded. Of note however, MADRS raters well To analyze scores, linear mixed-effects model conducted, factors group [sham (= reference), 1mA, 2mA], (BL, weeks 1–4, post), random intercepts slopes subjects: ∼1 | subject. showed significant week, demonstrating considerable reduction scores course BL (Fig. lack interaction [t (51) 0.09, p .946, B 0.04, SE 0.55] 0.22, .830, 0.12, indicates active groups different group. Two ANCOVAs, each two-level factor (sham vs. covariate score, no F (2, 28) 0.155, .679, ηp2 .006 marginal 29) 3.281, .080, .102 change FU: -18.29, 8.84, -12.93, 11.51. These do concept treatment MDD. Considering (for see Ref. Scholar]), likely specific design characteristics responsible difference between tDCS. First, contrast studies, days alternated stimulation-free days. Although intermitted schedule found promote neuroplasticity Scholar,[10]Ruf S.P. Fallgatter A.J. Augmentation (tDCS).Sci Rep. 2017; 876https://doi.org/10.1038/s41598-017-01055-1Crossref (82) Scholar], may have intensive enough patients. Second, allow better understanding relevant mechanisms positive refrained integrating our protocol. This leaves room possibility critical effect. note, medium sized tendency towards lower score than FU 1, 2), resembles similar patterns differences directly only FU. Moreover, accordance alone symptoms, observe substantial improvement across all study, which, least parts, effects. aspect important since small might obscured more prominent Taken together, add evidence CCT. modifications improve efficacy. consideration findings help inform research optimizing protocols work GCBS consortium (FKZ 01EE1403D awarded CP) funded German Federal Ministry Education Research .