Combined Cognitive Training and Transcranial Direct Current Stimulation in Neuropsychiatric Disorders: A Systematic Review and Meta-Analysis

Published:October 12, 2022DOI:



      Treatments for cognitive dysfunction in neuropsychiatric conditions are urgently needed. Cognitive training and transcranial direct current stimulation (tDCS) hold promise, and there is growing interest in combined or multi-modal treatments though studies to date have small samples and inconsistent results.


      A systematic review and meta-analysis was completed. Retained studies included cognitive training combined with active or sham tDCS in a neuropsychiatric population and reported a post-treatment cognitive outcome. Meta-analyses included effect sizes comparing cognitive training + active tDCS and cognitive training + sham tDCS in five cognitive domains. Risk of bias in included studies and across studies were explored.


      Fifteen studies were included; ten in neurodegenerative disorders and five in psychiatric disorders (n=629). There were several tDCS montages though two-thirds of studies placed the anode over left dorsolateral prefrontal cortex. A wide variety of cognitive training types and outcome measures were reported. There was a small, statistically significant effect of combined treatment on measures of attention/working memory, as well as small and non-statistically significant effects favoring combined treatment on global cognition and language. There was no evidence of bias in individual studies, but some evidence of non-reporting or small-study bias across studies.


      These results may provide preliminary support for the efficacy of combined cognitive training and tDCS on measures of attention/working memory. More data are needed, particularly via studies that explicitly align the cognitive ability of interest, stimulation target, training type, and outcome measures.


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        • Cloutier M.
        • Aigbogun M.S.
        • Guerin A.
        • Nitulescu R.
        • Ramanakumar A v
        • Kamat S.A.
        • et al.
        The Economic Burden of Schizophrenia in the United States in 2013.
        J Clin Psychiatry. 2016; 77: 764-771
        • Vossius C.
        • Larsen J.P.
        • Janvin C.
        • Aarsland D.
        The economic impact of cognitive impairment in Parkinson’s disease.
        Movement Disorders. 2011; 26: 1541-1544
        • Wong W.
        Economic Burden of Alzheimer Disease and Managed Care Considerations.
        American Journal of Managed Care. 2020; 26: S177
        • Cummings J.L.
        • Tong G.
        • Ballard C.
        Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options.
        Journal of Alzheimer’s Disease. 2019; 67: 779-794
      1. Harvey PD, Bowie CR (2012): Cognitive Enhancement in Schizophrenia: Pharmacological and Cognitive Remediation Approaches.

        • Prikken M.
        • Konings M.J.
        • Lei W.U.
        • Begemann M.J.H.
        • Sommer I.E.C.
        The efficacy of computerized cognitive drill and practice training for patients with a schizophrenia-spectrum disorder: A meta-analysis.
        Schizophrenia Research. 2019; 204: 368-374
        • Zhang H.
        • Huntley J.
        • Bhome R.
        • Holmes B.
        • Cahill J.
        • Gould R.L.
        • et al.
        Effect of computerised cognitive training on cognitive outcomes in mild cognitive impairment: a systematic review and meta-analysis.
        BMJ Open. 2019; 9
        • Hampstead B.M.
        • Sathian K.
        • Phillips P.A.
        • Amaraneni A.
        • Delaune W.R.
        • Stringer A.Y.
        Mnemonic Strategy Training Improves Memory for Object Location Associations in Both Healthy Elderly and Patients With Amnestic Mild Cognitive Impairment: A Randomized, Single-Blind Study.
        Neuropsychology. 2012; 26: 385-399
        • Allott K.
        • Van-Der-El K.
        • Bryce S.
        • Parrish E.M.
        • Mcgurk S.R.
        • Hetrick S.
        • et al.
        Compensatory Interventions for Cognitive Impairments in Psychosis: A Systematic Review and Meta-Analysis.
        Schizophrenia Bulletin. 2020; 46: 869-883
        • Bahar-Fuchs A.
        • Clare L.
        • Woods B.
        Cognitive training and cognitive rehabilitation for persons with mild to moderate dementia of the Alzheimer’s or vascular type: a review.
        Alzheimer’s Research & Therapy. 2013; 5: 1-14
      2. Bender A, Spat-Lemus J (2019): Cognitive Training and Rehabilitation in Aging and Dementia. In: Ravdin LD, Katzen HL, editors. Handbook on the Neuropsychology of Aging and Dementia. Springer Nature Switzerland, pp 365–387.

      3. Hampstead BM, Gillis MM, Stringer AY (2014): Cognitive rehabilitation of memory for mild cognitive impairment: A methodological review and model for future research. Journal of the International Neuropsychological Society, vol. 20. Cambridge University Press, pp 135–151.

        • Keshavan M.S.
        • Vinogradov S.
        • Rumsey J.
        • Sherrill J.
        • Wagner A.
        • Bar-Haim Y.
        Cognitive Training in Mental Disorders: Update and Future Directions.
        Am J Psychiatry. 2014; 171: 510-522
        • Kim E.J.
        • Bahk Y.-C.
        • Oh H.
        • Lee W.-H.
        • Lee J.S.
        • Choi K.-H.
        Current Status of Cognitive Remediation for Psychiatric Disorders: A Review.
        Frontiers in Psychiatry. 2018;
        • Rabipour S.
        • Raz A.
        Training the brain: Fact and fad in cognitive and behavioral remediation.
        Brain and Cognition. 2012, July; 79: 159-179
        • Wykes T.
        • Huddy V.
        • Cellard C.
        • McGurk S.
        • Czobor P.
        A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes.
        Am J Psychiatry. 2011; 168: 472-485
      4. Kurtz MM (2016): Cognitive Remediation for Psychological Disorders: An Overview. In: Medalia A, Bowie CR, editors. Cognitive Remediation to Improve Functional Outcomes. Oxford University Press, pp 1–23.

        • Sherman D.S.
        • Mauser J.
        • Nuno M.
        • Sherzai D.
        The Efficacy of Cognitive Intervention in Mild Cognitive Impairment (MCI): a Meta-Analysis of Outcomes on Neuropsychological Measures.
        Neuropsychology Review. 2017; 27: 440-484
        • Sitzer D.I.
        • Twamley E.W.
        • Jeste D v
        Cognitive training in Alzheimer’s disease: A meta-analysis of the literature.
        Acta Psychiatrica Scandinavica. 2006; 114: 75-90
      5. Antal A, Alekseichuk I, Bikson M, Brockmöller J, Brunoni AR, Chen R, et al. (2017, September 1): Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clinical Neurophysiology, vol. 128. Elsevier Ireland Ltd, pp 1774–1809.

      6. Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, et al. (2016, September 1): Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimulation, vol. 9. Elsevier Inc., pp 641–661.

        • Brunoni A.R.
        • Nitsche M.A.
        • Bolognini N.
        • Bikson M.
        • Wagner T.
        • Merabet L.
        • et al.
        Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions.
        Brain Stimulation. 2012, July; 5: 175-195
      7. Lefaucheur JP, Wendling F (2019, September 1): Mechanisms of action of tDCS: A brief and practical overview. Neurophysiologie Clinique, vol. 49. Elsevier Masson SAS, pp 269–275.

        • Nitsche M.A.
        • Cohen L.G.
        • Wassermann E.M.
        • Priori A.
        • Lang N.
        • Antal A.
        • et al.
        Transcranial direct current stimulation: State of the art 2008.
        Brain Stimulation. 2008; 1: 206-223
        • Nitsche M.A.
        • Paulus W.
        Transcranial direct current stimulation-update 2011.
        Restorative Neurology and Neuroscience. 2011; 29: 463-492
      8. Sudbrack-Oliveira P, Razza LB, Brunoni AR (2021): Non-invasive cortical stimulation: Transcranial direct current stimulation (tDCS). International Review of Neurobiology, vol. 159. Academic Press Inc., pp 1–22.

      9. Horvath JC, Forte JD, Carter O (2015, January 1): Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: A systematic review. Neuropsychologia, vol. 66. Elsevier Ltd, pp 213–236.

      10. Ciullo V, Spalletta G, Caltagirone C, Banaj N, Vecchio D, Piras F, Piras F (2021, June 1): Transcranial Direct Current Stimulation and Cognition in Neuropsychiatric Disorders: Systematic Review of the Evidence and Future Directions. Neuroscientist, vol. 27. SAGE Publications Inc., pp 285–309.

      11. Brunoni AR, Vanderhasselt M-A (2014): Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis.

      12. Mancuso LE, Ilieva IP, Hamilton RH, Farah MJ (2016): Does Transcranial Direct Current Stimulation Improve Healthy Working Memory?: A Meta-analytic Review.

        • Shin Y il
        • Foerster Á.
        • Nitsche M.A.
        Transcranial direct current stimulation (tDCS) - Application in neuropsychology.
        Neuropsychologia. 2015; 69: 154-175
      13. Fregni F, El-Hagrassy MM, Pacheco-Barrios K, Carvalho S, Leite J, Simis M, et al. (2021, April 1): Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders. International Journal of Neuropsychopharmacology, vol. 24. Oxford University Press, pp 256–313.

        • Aust S.
        • Brakemeier E.L.
        • Spies J.
        • Herrera-Melendez A.L.
        • Kaiser T.
        • Fallgatter A.
        • et al.
        Efficacy of Augmentation of Cognitive Behavioral Therapy with Transcranial Direct Current Stimulation for Depression: A Randomized Clinical Trial.
        JAMA Psychiatry. 2022; 79: 528-537
      14. Cruz Gonzalez P, Fong KNK, Chung RCK, Ting KH, Law LLF, Brown T (2018, October 16): Can transcranial direct-current stimulation alone or combined with cognitive training be used as a clinical intervention to improve cognitive functioning in persons with mild cognitive impairment and dementia? A systematic review and meta-analysis. Frontiers in Human Neuroscience, vol. 12. Frontiers Media S.A.

        • Inagawa T.
        • Narita Z.
        • Sugawara N.
        • Maruo K.
        • Stickley A.
        • Yokoi Y.
        • Sumiyoshi T.
        A Meta-Analysis of the Effect of Multisession Transcranial Direct Current Stimulation on Cognition in Dementia and Mild Cognitive Impairment.
        Clinical EEG and Neuroscience. 2019; 50: 273-282
      15. Teselink J, Bawa KK, Koo GK, Sankhe K, Liu CS, Rapoport M, et al. (2021, December 1): Efficacy of non-invasive brain stimulation on global cognition and neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment: A meta-analysis and systematic review. Ageing Research Reviews, vol. 72. Elsevier Ireland Ltd.

      16. Wang T, Guo Z, Du Y, Xiong M, Yang Z, Ren L, et al. (2021): Effects of Noninvasive Brain Stimulation (NIBS) on Cognitive Impairment in Mild Cognitive Impairment and Alzheimer Disease A Meta-Analysis. Retrieved from

        • Xu Y.
        • Qiu Z.
        • Zhu J.
        • Liu J.
        • Wu J.
        • Tao J.
        • Chen L.
        The modulation effect of non-invasive brain stimulation on cognitive function in patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.
        BMC Neuroscience. 2019; 20
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        BMJ. 2009; 339: b2535
        • Page M.J.
        • Mckenzie J.E.
        • Bossuyt P.M.
        • Boutron I.
        • Hoffmann T.C.
        • Mulrow C.D.
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
        • Clare L.
        • Woods R.T.
        Cognitive training and cognitive rehabilitation for people with early-stage Alzheimer’s disease: A review.
        Neuropsychological Rehabilitation. 2004; 14: 385-401
        • Sterne J.
        • Savovic J.
        • Page M.
        • Elbers R.
        • Blencowe N.
        • Boutron I.
        • et al.
        RoB 2: a revised tool for assessing risk of bias in randomised trials.
        BMJ. 2019; 36614898
      17. Review Manager (RevMan) [no. 5.4] (2020): The Cochrane Collaboration.

      18. Cohen J (2013): Statistical Power Analysis for the Behavioral Sciences, Second. Routledge.

      19. Deeks J, Higgins J, Altman D (2022): Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, Welch V, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 6.3.

      20. Page M, Higgins J, Sterne J (2022): Chapter 13: Assessing risk of bias due to missing results in a synthesis. In: Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, Welch V, editors. Cochrane Handbook for Systematic Reviews of Interventions, version 6.3.

        • Cotelli M.
        • Manenti R.
        • Petesi M.
        • Brambilla M.
        • Cosseddu M.
        • Zanetti O.
        • et al.
        Treatment of primary progressive aphasias by transcranial direct current stimulation combined with language training.
        Journal of Alzheimer’s Disease. 2014; 39: 799-808
      21. Biundo R, Weis L, Fiorenzato E, Gentile G, Giglio M, Schifano R, et al. (2015, November 1): Double-blind randomized trial of t-DCS versus sham in Parkinson patients with mild cognitive impairment receiving cognitive training. Brain Stimulation, vol. 8. Elsevier Inc., pp 1223–1225.

        • de Sousa A.V.C.
        • Grittner U.
        • Rujescu D.
        • Külzow N.
        • Flöel A.
        Impact of 3-Day Combined Anodal Transcranial Direct Current Stimulation-Visuospatial Training on Object-Location Memory in Healthy Older Adults and Patients with Mild Cognitive Impairment.
        Journal of Alzheimer’s Disease. 2020; 75: 223-244
        • Martin D.M.
        • Mohan A.
        • Alonzo A.
        • Gates N.
        • Gbadeyan O.
        • Meinzer M.
        • et al.
        A Pilot Double-Blind Randomized Controlled Trial of Cognitive Training Combined with Transcranial Direct Current Stimulation for Amnestic Mild Cognitive Impairment.
        Journal of Alzheimer’s Disease. 2019; 71: 503-512
        • Das N.
        • Spence J.S.
        • Aslan S.
        • Vanneste S.
        • Mudar R.
        • Rackley A.
        • et al.
        Cognitive training and transcranial direct current stimulation in mild cognitive impairment: A randomized pilot trial.
        Frontiers in Neuroscience. 2019; 13
        • Cotelli M.
        • Manenti R.
        • Petesi M.
        • Brambilla M.
        • Rosini S.
        • Ferrari C.
        • et al.
        Anodal tDCS during face-name associations memory training in Alzheimer’s patients.
        Frontiers in Aging Neuroscience. 2014; 6
        • Lu H.
        • Chan S.S.M.
        • Chan W.C.
        • Lin C.
        • Cheng C.P.W.
        • Linda Chiu Wa L.
        Randomized controlled trial of TDCS on cognition in 201 seniors with mild neurocognitive disorder.
        Annals of Clinical and Translational Neurology. 2019; 6: 1938-1948
        • Inagawa T.
        • Yokoi Y.
        • Narita Z.
        • Maruo K.
        • Okazaki M.
        • Nakagome K.
        Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study.
        Frontiers in Human Neuroscience. 2019; 13
        • Manenti R.
        • Cotelli M.S.
        • Cobelli C.
        • Gobbi E.
        • Brambilla M.
        • Rusich D.
        • et al.
        Transcranial direct current stimulation combined with cognitive training for the treatment of Parkinson Disease: A randomized, placebo-controlled study.
        Brain Stimulation. 2018; 11: 1251-1262
        • Roncero C.
        • Kniefel H.
        • Service E.
        • Thiel A.
        • Probst S.
        • Chertkow H.
        Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer’s disease and frontotemporal dementia.
        Alzheimer’s and Dementia: Translational Research and Clinical Interventions. 2017; 3: 247-253
      22. Nienow TM, MacDonald AW, Lim KO (2016, April 1): TDCS produces incremental gain when combined with working memory training in patients with schizophrenia: A proof of concept pilot study. Schizophrenia Research, vol. 172. Elsevier B.V., pp 218–219.

        • Orlov N.D.
        • Tracy D.K.
        • Joyce D.
        • Patel S.
        • Rodzinka-Pasko J.
        • Dolan H.
        • et al.
        Stimulating cognition in schizophrenia: A controlled pilot study of the effects of prefrontal transcranial direct current stimulation upon memory and learning.
        Brain Stimulation. 2017; 10: 560-566
        • Segrave R.A.
        • Arnold S.
        • Hoy K.
        • Fitzgerald P.B.
        Concurrent cognitive control training augments the antidepressant efficacy of tDCS: A pilot study.
        Brain Stimulation. 2014; 7: 325-331
        • Vanderhasselt M.A.
        • de Raedt R.
        • Namur V.
        • Lotufo P.A.
        • Bensenor I.M.
        • Boggio P.S.
        • Brunoni A.R.
        Transcranial electric stimulation and neurocognitive training in clinically depressed patients: A pilot study of the effects on rumination.
        Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2015; 57: 93-99
        • Xu X.
        • Ding X.
        • Chen L.
        • Chen T.
        • Su H.
        • Li X.
        • et al.
        The transcranial direct current stimulation over prefrontal cortex combined with the cognitive training reduced the cue-induced craving in female individuals with methamphetamine use disorder: A randomized controlled trial.
        Journal of Psychiatric Research. 2021; 134: 102-110
        • Leucht S.
        • Helfer B.
        • Gartlehner G.
        • Davis J.M.
        How effective are common medications: a perspective based on meta-analyses of major drugs.
        BMC Medicine. 2015;
        • Woods A.J.
        • Antal A.
        • Bikson M.
        • Boggio P.S.
        • Brunoni A.R.
        • Celnik P.
        • et al.
        A technical guide to tDCS, and related non-invasive brain stimulation tools guide Methodology review Safety Design h i g h l i g h t s.
        Clinical Neurophysiology. 2016; 127: 1031-1048
        • Reckow J.
        • Rahman-Filipiak A.
        • Garcia S.
        • Schlaefflin S.
        • Calhoun O.
        • DaSilva A.F.
        • et al.
        Tolerability and blinding of 4×1 High-Definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps.
        Brain Stimulation. 2018; 11: 991-997
        • Lang N.
        • Siebner H.R.
        • Ward N.S.
        • Lee L.
        • Nitsche M.A.
        • Paulus W.
        • et al.
        How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?.
        European Journal of Neuroscience. 2005; 22: 495-504
        • Nitsche M.A.
        • Doemkes S.
        • Karaköse T.
        • Antal A.
        • Liebetanz D.
        • Lang N.
        • et al.
        Shaping the effects of transcranial direct current stimulation of the human motor cortex.
        Journal of Neurophysiology. 2007; 97: 3109-3117
        • Datta A.
        • Truong D.
        • Minhas P.
        • Parra L.C.
        • Bikson M.
        • Brunoni A.R.
        • et al.
        Inter-individual variation during transcranial direct current stimulation and normalization of dose using MRI-derived computational models.
        Frontiers in Psychiatry. 2012; 3: 1-8
        • Horvath J.C.
        • Carter O.
        • Forte J.D.
        • Lebedev M.
        • Vicario C.M.
        Transcranial direct current stimulation: five important issues we aren’t discussing (but probably should be).
        Frontiers in System Neuroscience. 2014; 8: 1-8
      23. Garnett EO, Malyutina S, Datta A, Dirk-Bart Den Ouden ; (2015): On the Use of the Terms Anodal and Cathodal in High-Definition Transcranial Direct Current Stimulation: A Technical Note.

        • Mosayebi Samani M.
        • Agboada D.
        • Jamil A.
        • Kuo M.F.
        • Nitsche M.A.
        Titrating the neuroplastic effects of cathodal transcranial direct current stimulation (tDCS) over the primary motor cortex.
        Cortex. 2019; 119: 350-361
        • Datta A.
        • Bansal V.
        • Diaz J.
        • Patel J.
        • Reato D.
        • Bikson M.
        Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad.
        Brain Stimulation. 2009; 2
        • Kuo H.I.
        • Bikson M.
        • Datta A.
        • Minhas P.
        • Paulus W.
        • Kuo M.F.
        • Nitsche M.A.
        Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: A neurophysiological study.
        Brain Stimulation. 2013; 6: 644-648
        • Fridriksson J.
        • Rorden C.
        • Elm J.
        • Sen S.
        • George M.S.
        • Bonilha L.
        Transcranial Direct Current Stimulation vs Sham Stimulation to Treat Aphasia After Stroke A Randomized Clinical Trial.
        JAMA Neurol. 2018; 75: 1470-1476