Non-invasive brain stimulation for the treatment of neurological and psychiatric disorders and for improving physical performance: protocol of umbrella reviews

protocolo de revisões guarda-chuva




Transcranial magnetic stimulation, Transcranial direct current stimulation, Evidence-based medicine, Systematic review


Background: With the increasing meta-analysis studies of noninvasive brain stimulation (NIBS) a major review has become a logical step to provide evidence to support decision-makers. Objective: Umbrella reviews of the Working-Group of NAPeN Network (a Brazilian scientific network for NIBS development) will summarize the results of existing evidence in meta-analysis with focus on NIBS techniques applied for clinical settings, exercise and sports science. Methods and materials:  Firstly, a screening was performed to identify meta-analysis in which NIBS were applied to neurological and psychiatric disorders and healthy subjects. A second literature search was conducted in the Pubmed using a PICO-question for each population and NIBS techniques found in the first search. Methodological quality and certainty of evidence will be evaluated using the AMSTAR 2 and GRADE framework, respectively. Partial results: After the first search, we found meta-analyses including repetitive transcranial magnetic stimulation and transcranial direct current stimulation, applied in populations with neurological (cerebral palsy, chronic pain, dementia, epilepsy, essential tremor, multiple sclerosis, Parkinson’s disease, tinnitus, tourette syndrome, and stroke) and psychiatric disorders (anxiety, attention-deficit hyperactivity, autism spectrum, obsessive-compulsive and post-traumatic stress disorders, schizophrenia, craving/addiction and depression), and in healthy subjects. A total of 118 meta-analyses will be included in the qualitative review. The results of evidence were identified in the outcomes of six umbrella reviews. Conclusion:  Evidence of therapeutic and nontherapeutic use of NIBS techniques will support experts to produce consensus statements and assist professionals in making decisions of incorporating or not NIBS into clinical practice.


(1) Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017;128(1):56–92.

(2) Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018). Clin Neurophysiol. 2020;131(2):474–528.

(3) Terranova C, Rizzo V, Cacciola A, Chillemi G, Calamuneri A, Milardi D, et al. Is There a Future for Non-invasive Brain Stimulation as a Therapeutic Tool? Front Neurol. 2018;9:1146.

(4) Zimerman M, Hummel FC. Brain Stimulation and its Role in Neurological Diseases. In: Cohen Kadosh R, editor. The Stimulated Brain. San Diego: Academic Press; 2014. p. 333–69.

(5) Brunoni AR, Sampaio-Junior B, Moffa AH, Aparício LV, Gordon P, Klein I, et al. Noninvasive brain stimulation in psychiatric disorders: a primer. Braz J Psychiatry. 2019 Jan;41(1):70–81.

(6) Morya E, Monte-Silva K, Bikson M, Esmaeilpour Z, Biazoli CE Jr, Fonseca A, et al. Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes. J Neuroeng Rehabil. 2019 Nov 15;16(1):141.

(7) Angius L, Pascual-Leone A, Santarnecchi E. Brain stimulation and physical performance. Prog Brain Res. 2018;240:317–39.

(8) Okano AH, Fontes EB, Montenegro RA, Farinatti PTV, Cyrino ES, Li LM, et al. Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise. Br J Sports Med . 2015;49(18).

(9) Machado DGS, Unal G, Andrade SM, Moreira A, Altimari LR, Brunoni AR, et al. Effect of transcranial direct current stimulation on exercise performance: A systematic review and meta-analysis. Brain Stimul. 2019;12(3):593–605.

(10) Moreira A, Machado DGS, Moscaleski L, Bikson M, Unal G, Bradley PS, et al. Effect of tDCS on well-being and autonomic function in professional male players after official soccer matches. Physiol Behav. 2021;233:113351.

(11) Boes AD, Kelly MS, Trapp NT, Stern AP, Press DZ, Pascual-Leone A. Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty. J Neuropsychiatry Clin Neurosci. 2018;30(3):173–9.

(12) Gellner AK, Reis J, Fritsch B. Glia: A Neglected Player in Non-invasive Direct Current Brain Stimulation. Front Cell Neurosci. 2016;10:188

(13) Romero MC, Davare M, Armendariz M, Janssen P. Neural effects of transcranial magnetic stimulation at the single-cell level. Nat Commun. 2019;10:2642.

(14) Valero-Cabré A, Amengual JL, Stengel C, Pascual-Leone A, Coubard OA. Transcranial magnetic stimulation in basic and clinical neuroscience: A comprehensive review of fundamental principles and novel insights. Neurosci Biobehav Rev. 2017;83:381–404.

(15) Sale MV, Mattingley JB, Zalesky A, Cocchi L. Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation. Neurosci Biobehav Rev. 2015;57:187–98.

(16) Baptista AF, Fernandes AMBL, Sá KN, Okano AH, Brunoni AR, Lara-Solares A, et al. Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP). Pain Rep. 2019;4(1):e692.

(17) Shirahige L, Melo L, Nogueira F, Rocha S, Monte-Silva K. Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A Systematic Review and Meta-Analysis. Headache. 2016;56(10):1565–96.

(18) Xiang H, Sun J, Tang X, Zeng K, Wu X. The effect and optimal parameters of repetitive transcranial magnetic stimulation on motor recovery in stroke patients: a systematic review and meta-analysis of randomized controlled trials. Clin Rehabil. 2019;33(5):847–64.

(19) Allida S, Cox KL, Hsieh C, Lang H, House A, Hackett ML. Pharmacological, psychological, and non-invasive brain stimulation interventions for treating depression after stroke. Cochrane Database Syst Rev. 2020;1(1):CD003437.

(20) Bucur M, Papagno C. Are transcranial brain stimulation effects long-lasting in post-stroke aphasia? A comparative systematic review and meta-analysis on naming performance. Neurosci Biobehav Rev. 2019;102:264–89.

(21) Salazar APS, Vaz PG, Marchese RR, Stein C, Pinto C, Pagnussat AS. Noninvasive Brain Stimulation Improves Hemispatial Neglect After Stroke: A Systematic Review and Meta-Analysis. Arch Phys Med Rehabil. 2018;99(2):355–66.e1.

(22) Kang N, Summers JJ, Cauraugh JH. Transcranial direct current stimulation facilitates motor learning post-stroke: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87(4):345–55.

(23) Vacas SM, Stella F, Loureiro JC, Couto FS, Oliveira-Maia AJ, Forlenza OV. Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: A systematic review and meta-analysis. Int J Geriatr Psychiatry. 2019;34(9):1336–45.

(24) Goodwill AM, Lum JAG, Hendy AM, Muthalib M, Johnson L, Albein-Urios N, et al. Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson’s disease: a systematic review and meta-analysis. Sci Rep. 2017;7(1):14840.

(25) Liu M, Fan S, Xu Y, Cui L. Non-invasive brain stimulation for fatigue in multiple sclerosis patients: A systematic review and meta-analysis. Mult Scler Relat Disord. 2019;36:101375.

(26) Razza LB, Palumbo P, Moffa AH, Carvalho AF, Solmi M, Loo CK, et al. A systematic review and meta-analysis on the effects of transcranial direct current stimulation in depressive episodes. Depress Anxiety. 2020;37(7):594–608.

(27) Moffa AH, Martin D, Alonzo A, Bennabi D, Blumberger DM, Benseñor IM, et al. Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2020;99:109836.

(28) Cirillo P, Gold AK, Nardi AE, Ornelas AC, Nierenberg AA, Camprodon J, et al. Transcranial magnetic stimulation in anxiety and trauma-related disorders: A systematic review and meta-analysis. Brain Behav. 2019;9(6):e01284.

(29) Kedzior KK, Gellersen HM, Roth Y, Zangen A. Acute reduction in anxiety after deep transcranial magnetic stimulation (DTMS) in unipolar major depression- a systematic review and meta-analysis. Psychiatry Res. 2015;230(3):971–4.

(30) Cocchi L, Zalesky A, Nott Z, Whybird G, Fitzgerald PB, Breakspear M. Transcranial magnetic stimulation in obsessive-compulsive disorder: A focus on network mechanisms and state dependence. Neuroimage Clin. 2018;19:661–74.

(31) Zhou DD, Wang W, Wang GM, Li DQ, Kuang L. An updated meta-analysis: Short-term therapeutic effects of repeated transcranial magnetic stimulation in treating obsessive-compulsive disorder. J Affect Disord. 2017;215:187–96.

(32) Kennedy NI, Lee WH, Frangou S. Efficacy of non-invasive brain stimulation on the symptom dimensions of schizophrenia: A meta-analysis of randomized controlled trials. Eur Psychiatry. 2018;49:69–77.

(33) Aleman A, Enriquez-Geppert S, Knegtering H, Dlabac-de Lange JJ. Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials. Neurosci Biobehav Rev. 2018;89:111–8.

(34) Chen J, Qin J, He Q, Zou Z. A Meta-Analysis of Transcranial Direct Current Stimulation on Substance and Food Craving: What Effect Do Modulators Have? Front Psychiatry. 2020;11:598.

(35) Ma T, Sun Y, Ku Y. Effects of Non-invasive Brain Stimulation on Stimulant Craving in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-Analysis. Front Neurosci. 2019;13:1095.

(36) Holgado D, Vadillo MA, Sanabria D. The effects of transcranial direct current stimulation on objective and subjective indexes of exercise performance: A systematic review and meta-analysis. Brain Stimul. 2019;12(2):242–50.

(37) Lattari E, Oliveira BRR, Monteiro Júnior RS, Marques Neto SR, Oliveira AJ, Maranhão Neto GA, et al. Acute effects of single dose transcranial direct current stimulation on muscle strength: A systematic review and meta-analysis. PLoS One. 2018;13(12):e0209513.

(38) Hazime FA, Cunha RA, Soliaman RR, Romancini ACB, Pochini AC, Ejnisman B, et al. Anodal transcranial direct current stimulation (tdcs) increases isometric strength of shoulder rotators muscles in handball players. Int J Sports Phys Ther. 2017;12(3):402–7. Cited: PMID: 28593094

(39) Fregni F, Nitsche MA, Loo CK, Brunoni AR, Marangolo P, Leite J, et al. Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. Clin Res Regul Aff. 2015;32(1):22–35.

(40) James D, Warren-Forward H. Research methods for formal consensus development. Nurse Res. 2015;22(3):35–40.

(41) Murphy MK, Black NA, Lamping DL, McKee CM, Sanderson CF, Askham J, et al. Consensus development methods, and their use in clinical guideline development. Health Technol Assess. 1998;2(3):i-iv,1-88.

(42) Aromataris E, Fernandez R, Godfrey CM, Holly C, Khalil H, Tungpunkom P. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach. Int J Evid Based Healthc. 2015;13(3):132–40.

(43) Fusar-Poli P, Radua J. Ten simple rules for conducting umbrella reviews. Evid Based Ment Health. 2018;21(3):95–100.

(44) Razza LB, Afonso Dos Santos L, Borrione L, Bellini H, Branco LC, Cretaz E, et al. Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials. Braz J Psychiatry. 2021;43(5):514–24.

(45) Farhat LC, Carvalho AF, Solmi M, Brunoni AR. Evidence-based umbrella review of cognitive effects of prefrontal tDCS. Soc Cogn Affect Neurosci. 2022;17(1):43-60.

(46) Rosson S, Filippis R, Croatto G, Collantoni E, Pallottino S, Guinart D, et al. Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review. Neurosci Biobehav Rev. 2022;139:104743.

(47) Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008.

(48) Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). J Clin Epidemiol. 2011;64(4):407–15.

(49) Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–6.

(50) Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol. 2011;64(4):395–400.

(51) Ioannidis J. Next-generation systematic reviews: prospective meta-analysis, individual-level data, networks and umbrella reviews. Br J Sports Med. 2017;51:1456-1458.

(52) Xie J, Geng X, Fan F, Fu X, He S, Li T. The efficacy of therapies for post-stroke depression in aging: An umbrella review. Front Aging Neurosci. 2022;14:993250.

(53) Millar JD, van Wijck F, Pollock A, Ali M. Outcome measures in post-stroke arm rehabilitation trials: do existing measures capture outcomes that are important to stroke survivors, carers, and clinicians? Clin Rehabil. 2019;33(4):737-749.







How to Cite

Shirahige L, Baptista A, Sá KN, Baltar A, Marques D, Carneiro MS, et al. Non-invasive brain stimulation for the treatment of neurological and psychiatric disorders and for improving physical performance: protocol of umbrella reviews: protocolo de revisões guarda-chuva. Brain Imaging and Stimul. [Internet]. 2022 Nov. 16 [cited 2024 May 22];1:e4400. Available from:

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