Increased leg muscle fatigability during 2 mA and 4 mA transcranial direct current stimulation over the left motor cortex

  • Craig D. Workman
  • John Kamholz
  • Thorsten RudroffEmail author
Research Article


Transcranial direct current stimulation (tDCS) using intensities ≤ 2 mA on physical and cognitive outcomes has been extensively investigated. Studies comparing the effects of different intensities of tDCS have yielded mixed results and little is known about how higher intensities (> 2 mA) affect outcomes. This study examined the effects of tDCS at 2 mA and 4 mA on leg muscle fatigability. This was a double-blind, randomized, sham-controlled study. Sixteen healthy young adults underwent tDCS at three randomly ordered intensities (sham, 2 mA, 4 mA). Leg muscle fatigability of both legs was assessed via isokinetic fatigue testing (40 maximal reps, 120°/s). Torque- and work-derived fatigue indices (FI-T and FI-W, respectively), as well as total work performed (TW), were calculated. FI-T of the right knee extensors indicated increased fatigability in 2 mA and 4 mA compared with sham (p = 0.01, d = 0.73 and p < 0.001, d = 1.61, respectively). FI-W of the right knee extensors also indicated increased fatigability in 2 mA and 4 mA compared to sham (p = 0.01, d = 0.57 and p < 0.001, d = 1.12, respectively) and 4 mA compared with 2 mA (p = 0.034, d = 0.37). tDCS intensity did not affect TW performed. The 2 mA and 4 mA tDCS intensities increased the fatigability of the right knee extensors in young, healthy participants, potentially from altered motor unit recruitment/discharge rate or cortical hyperexcitability. Despite this increase in fatigability, the TW performed in both these conditions was not different from sham.


Non-invasive brain stimulation Transcranial direct current stimulation Muscle fatigue High intensity Isokinetic task 



We thank the study participants for their effort and time. In addition, we thank Emily Jester, Veronica Smith, and Delaney McDowell for their assistance in data collection. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


  1. Abdelmoula A, Baudry S, Duchateau J (2016) Anodal transcranial direct current stimulation enhances time to task failure of a submaximal contraction of elbow flexors without changing corticospinal excitability. Neuroscience 322:94–103. CrossRefPubMedGoogle Scholar
  2. Alix-Fages C et al (2019) Short-term effects of anodal transcranial direct current stimulation on endurance and maximal force production. A systematic review and meta-analysis. J Clin Med. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ammann C, Spampinato D, Marquez-Ruiz J (2016) Modulating motor learning through transcranial direct-current stimulation: an integrative view. Front Psychol 7:1981. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Ammann C, Lindquist MA, Celnik PA (2017) Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions. Brain Stimulat 10:757–763. CrossRefGoogle Scholar
  5. Andrade C (2013) Once- to twice-daily, 3-year domiciliary maintenance transcranial direct current stimulation for severe, disabling, clozapine-refractory continuous auditory hallucinations in schizophrenia. J ECT 29:239–242. CrossRefPubMedGoogle Scholar
  6. Angius L, Pageaux B, Hopker J, Marcora SM, Mauger AR (2016) Transcranial direct current stimulation improves isometric time to exhaustion of the knee extensors. Neuroscience 339:363–375. CrossRefPubMedGoogle Scholar
  7. Angius L, Hopker J, Mauger AR (2017) The ergogenic effects of transcranial direct current stimulation on exercise performance. Front Physiol 8:90. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Angius L, Mauger AR, Hopker J, Pascual-Leone A, Santarnecchi E, Marcora SM (2018a) Bilateral extracephalic transcranial direct current stimulation improves endurance performance in healthy individuals. Brain Stimulat 11:108–117. CrossRefGoogle Scholar
  9. Angius L, Pascual-Leone A, Santarnecchi E (2018b) Brain stimulation and physical performance. Prog Brain Res 240:317–339. CrossRefPubMedGoogle Scholar
  10. Aparicio LVM, Guarienti F, Razza LB, Carvalho AF, Fregni F, Brunoni AR (2016) A systematic review on the acceptability and tolerability of transcranial direct current stimulation treatment in neuropsychiatry trials. Brain Stimulat 9:671–681. CrossRefGoogle Scholar
  11. Bastani A, Jaberzadeh S (2013a) Differential modulation of corticospinal excitability by different current densities of anodal transcranial direct current stimulation. PLoS ONE 8:e72254. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bastani A, Jaberzadeh S (2013b) The a-tDCS differential modulation of corticospinal excitability: the effects of electrode size Brain stimulation 6:932–937. CrossRefPubMedGoogle Scholar
  13. Batsikadze G, Moliadze V, Paulus W, Kuo MF, Nitsche MA (2013) Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. J Physiol 591:1987–2000. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Berryhill ME, Martin D (2018) Cognitive effects of transcranial direct current stimulation in healthy and clinical populations: an overview. J ECT 34:e25–e35. CrossRefPubMedGoogle Scholar
  15. Bikson M et al (2016) Safety of transcranial direct current stimulation: evidence based update. Brain Stimulat 9:641–661. CrossRefGoogle Scholar
  16. Bindman LJ, Lippold OC, Redfearn JW (1964) The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects. J Physiol 172:369–382. CrossRefPubMedPubMedCentralGoogle Scholar
  17. Cancelli A et al (2018) Personalized, bilateral whole-body somatosensory cortex stimulation to relieve fatigue in multiple sclerosis. Multiple Sclerosis (Houndmills, Basingstoke, England) 24:1366–1374. CrossRefGoogle Scholar
  18. Chai Z, Ma C, Jin X (2019) Cortical stimulation for treatment of neurological disorders of hyperexcitability: a role of homeostatic plasticity. Neural Regen Res 14:34–38. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Chew T, Ho KA, Loo CK (2015) Inter- and intra-individual variability in response to transcranial direct current stimulation (tDCS) at varying current intensities. Brain Stimulat 8:1130–1137. CrossRefGoogle Scholar
  20. Chhatbar PY, Chen R, Deardorff R, Dellenbach B, Kautz SA, George MS, Feng W (2017) Safety and tolerability of transcranial direct current stimulation to stroke patients—a phase I current escalation study. Brain Stimulat 10:553–559. CrossRefGoogle Scholar
  21. Chhatbar PY et al (2018) Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo. Brain Stimulat 11:727–733. CrossRefGoogle Scholar
  22. Ciccone AB, Deckert JA, Schlabs CR, Tilden MJ, Herda TJ, Gallagher PM, Weir JP (2019) Transcranial direct current stimulation of the temporal lobe does not affect high-intensity work capacity. J Strength Cond Res 33:2074–2086. CrossRefPubMedGoogle Scholar
  23. Cogiamanian F, Marceglia S, Ardolino G, Barbieri S, Priori A (2007) Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas. Eur J Neurosci 26:242–249. CrossRefPubMedGoogle Scholar
  24. Dissanayaka T, Zoghi M, Farrell M, Egan GF, Jaberzadeh S (2017) Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta-analysis. Eur J Neurosci 46:1968–1990. CrossRefPubMedGoogle Scholar
  25. Esmaeilpour Z, Marangolo P, Hampstead BM, Bestmann S, Galletta E, Knotkova H, Bikson M (2018) Incomplete evidence that increasing current intensity of tDCS boosts outcomes. Brain Stimulat 11:310–321. CrossRefGoogle Scholar
  26. Ferrucci R et al (2014) Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis. NeuroRehabilitation 34:121–127. CrossRefPubMedGoogle Scholar
  27. Fertonani A, Ferrari C, Miniussi C (2015) What do you feel if I apply transcranial electric stimulation? Safety, sensations and secondary induced effects. Clin Neurophysiol 126:2181–2188. CrossRefPubMedGoogle Scholar
  28. Finsterer J, Mahjoub SZ (2014) Fatigue in healthy and diseased individuals. Am J Hosp Palliat Care 31:562–575. CrossRefPubMedGoogle Scholar
  29. Flood A, Waddington G, Keegan RJ, Thompson KG, Cathcart S (2017) The effects of elevated pain inhibition on endurance exercise performance. PeerJ 5:e3028. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Foerster ÁS, Rezaee Z, Paulus W, Nitsche MA, Dutta A (2018) Effects of cathode location and the size of anode on anodal transcranial direct current stimulation over the leg motor area in healthy humans. Front Neurosci 12:443–443. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Fujiyama H et al (2017) Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults. Neurobiol Aging 51:31–42. CrossRefPubMedGoogle Scholar
  32. Gleeson NP, Mercer TH (1992) Reproducibility of isokinetic leg strength and endurance characteristics of adult men and women. Eur J Appl Physiol Occup Physiol 65:221–228. CrossRefPubMedGoogle Scholar
  33. Gur H, Akova B, Punduk Z, Kucukoglu S (1999) Effects of age on the reciprocal peak torque ratios during knee muscle contractions in elite soccer players. Scand J Med Sci Sports 9:81–87CrossRefGoogle Scholar
  34. Hameau S, Bensmail D, Roche N, Zory R (2018) Adaptations of fatigue and fatigability after a short intensive, combined rehabilitation program in patients with multiple sclerosis. J Rehabilit Med 50:59–66. CrossRefGoogle Scholar
  35. Henneman E (1957) Relation between size of neurons and their susceptibility to discharge. Science 126:1345–1347. CrossRefPubMedGoogle Scholar
  36. Ho KA et al (2016) The effect of transcranial direct current stimulation (tDCS) electrode size and current intensity on motor cortical excitability: evidence from single and repeated sessions. Brain Stimulat 9:1–7. CrossRefGoogle Scholar
  37. Hoy KE, Arnold SL, Emonson MR, Daskalakis ZJ, Fitzgerald PB (2014) An investigation into the effects of tDCS dose on cognitive performance over time in patients with schizophrenia. Schizophr Res 155:96–100. CrossRefPubMedGoogle Scholar
  38. Jang H, Lee JY, Lee KI, Park KM (2017) Are there differences in brain morphology according to handedness? Brain Behav 7:e00730. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Jayaram G, Stinear JW (2009) The effects of transcranial stimulation on paretic lower limb motor excitability during walking. J Clin Neurophysiol 26:272–279. CrossRefPubMedGoogle Scholar
  40. Kan B, Dundas JE, Nosaka K (2013) Effect of transcranial direct current stimulation on elbow flexor maximal voluntary isometric strength and endurance. Appl Physiol Nutr Metab 38:734–739. CrossRefPubMedGoogle Scholar
  41. Kessler SK, Turkeltaub PE, Benson JG, Hamilton RH (2012) Differences in the experience of active and sham transcranial direct current stimulation. Brain Stimulat 5:155–162. CrossRefGoogle Scholar
  42. Khadka N et al (2019) Adaptive current tDCS up to 4 mA. Brain Stimul. CrossRefPubMedGoogle Scholar
  43. Kidgell DJ et al (2013) Different current intensities of anodal transcranial direct current stimulation do not differentially modulate motor cortex plasticity. Neural Plast 2013:603502. CrossRefPubMedPubMedCentralGoogle Scholar
  44. Klem GH, Luders HO, Jasper HH, Elger C (1999) The 10–20 electrode system of the International Federation. Int Feder Clin Neurophysiol Electroencephalogr Clin Neurophysiol Suppl 52:3–6Google Scholar
  45. Kluger BM, Krupp LB, Enoka RM (2013) Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology 80:409–416. CrossRefPubMedPubMedCentralGoogle Scholar
  46. Kollock R, Van Lunen BL, Ringleb SI, Onate JA (2015) Measures of functional performance and their association with hip and thigh strength. J Athl Train 50:14–22. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Krishnan C, Ranganathan R, Kantak SS, Dhaher YY, Rymer WZ (2014) Anodal transcranial direct current stimulation alters elbow flexor muscle recruitment strategies. Brain Stimulat 7:443–450. CrossRefGoogle Scholar
  48. Kuo MF, Paulus W, Nitsche MA (2014) Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases. Neuroimage 85(Pt 3):948–960. CrossRefPubMedGoogle Scholar
  49. Lambert CP, Archer RL, Evans WJ (2001) Muscle strength and fatigue during isokinetic exercise in individuals with multiple sclerosis. Med Sci Sports Exerc 33:1613–1619CrossRefGoogle Scholar
  50. Lattari E, de Oliveira BS, Oliveira BRR, de Mello Pedreiro RC, Machado S, Neto GAM (2018) Effects of transcranial direct current stimulation on time limit and ratings of perceived exertion in physically active women. Neurosci Lett 662:12–16. CrossRefPubMedGoogle Scholar
  51. Lee J et al (2019) Different brain connectivity between responders and nonresponders to dual-mode noninvasive brain stimulation over bilateral primary motor cortices in stroke patients. Neural Plast 2019:3826495. CrossRefPubMedPubMedCentralGoogle Scholar
  52. Lefaucheur JP, Chalah MA, Mhalla A, Palm U, Ayache SS, Mylius V (2017) The treatment of fatigue by non-invasive brain stimulation. Neurophysiol Clin Clin Neurophysiol 47:173–184. CrossRefGoogle Scholar
  53. Liew SL, Santarnecchi E, Buch ER, Cohen LG (2014) Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery. Front Hum Neurosci 8:378. CrossRefPubMedPubMedCentralGoogle Scholar
  54. Liu X et al (2018) Increased interhemispheric synchrony underlying the improved athletic performance of rowing athletes by transcranial direct current stimulation. Brain Imaging Behav. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Mackey CS, Thiele RM, Conchola EC, DeFreitas JM (2018) Comparison of fatigue responses and rapid force characteristics between explosive- and traditional-resistance-trained males. Eur J Appl Physiol 118:1539–1546. CrossRefPubMedGoogle Scholar
  56. Martin DM, Liu R, Alonzo A, Green M, Loo CK (2014) Use of transcranial direct current stimulation (tDCS) to enhance cognitive training: effect of timing of stimulation. Exp Brain Res 232:3345–3351. CrossRefPubMedGoogle Scholar
  57. Mellor JR, Randall AD (1998) Voltage-dependent deactivation and desensitization of GABA responses in cultured murine cerebellar granule cells. J Physiol 506(Pt 2):377–390. CrossRefPubMedPubMedCentralGoogle Scholar
  58. Montenegro R, Okano A, Gurgel J, Porto F, Cunha F, Massaferri R, Farinatti P (2015) Motor cortex tDCS does not improve strength performance in healthy subjects. Motriz Revista de Educação Física 21:185–193CrossRefGoogle Scholar
  59. Monte-Silva K, Kuo MF, Hessenthaler S, Fresnoza S, Liebetanz D, Paulus W, Nitsche MA (2013) Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimulat 6:424–432. CrossRefGoogle Scholar
  60. Murray LM, Edwards DJ, Ruffini G, Labar D, Stampas A, Pascual-Leone A, Cortes M (2015) Intensity dependent effects of transcranial direct current stimulation on corticospinal excitability in chronic spinal cord injury. Arch Phys Med Rehabil 96:S114–121. CrossRefPubMedGoogle Scholar
  61. Muthalib M, Kan B, Nosaka K, Perrey S (2013) Effects of transcranial direct current stimulation of the motor cortex on prefrontal cortex activation during a neuromuscular fatigue task: an fNIRS study. Adv Exp Med Biol 789:73–79. CrossRefPubMedGoogle Scholar
  62. Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527(Pt 3):633–639. CrossRefPubMedPubMedCentralGoogle Scholar
  63. Nitsche MA, Paulus W (2001) Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57:1899–1901. CrossRefPubMedGoogle Scholar
  64. Nitsche MA, Paulus W (2011) Transcranial direct current stimulation—update 2011. Restor Neurol Neurosci 29:463–492. CrossRefPubMedGoogle Scholar
  65. Nitsche MA et al (2008) Transcranial direct current stimulation: state of the art. Brain Stimulat 1:206–223. CrossRefGoogle Scholar
  66. Oconnell NE, Cossar J, Marston L, Wand BM, Bunce D, Moseley GL, De Souza LH (2012) Rethinking clinical trials of transcranial direct current stimulation: participant and assessor blinding is inadequate at intensities of 2mA. PLoS ONE 7:e47514–e47514. CrossRefGoogle Scholar
  67. Okano AH et al (2015) Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise. Br J Sports Med 49:1213–1218. CrossRefPubMedGoogle Scholar
  68. Oki K, Mahato NK, Nakazawa M, Amano S, France CR, Russ DW, Clark BC (2016) Preliminary evidence that excitatory transcranial direct current stimulation extends time to task failure of a sustained submaximal muscular contraction in older adults. J Gerontol A Biol Sci Med Sci 71:1109–1112. CrossRefPubMedPubMedCentralGoogle Scholar
  69. Papazova I et al (2018) Improving working memory in schizophrenia: effects of 1mA and 2mA transcranial direct current stimulation to the left DLPFC. Schizophr Res 202:203–209. CrossRefPubMedGoogle Scholar
  70. Player MJ et al (2014) Increase in PAS-induced neuroplasticity after a treatment course of transcranial direct current stimulation for depression. J Affect Disord 167:140–147. CrossRefPubMedGoogle Scholar
  71. Purpura DP, McMurtry JG (1965) Intracellular activities and evoked potential changes during polarization of motor cortex. J Neurophysiol 28:166–185. CrossRefPubMedGoogle Scholar
  72. Radel R, Tempest G, Denis G, Besson P, Zory R (2017) Extending the limits of force endurance: stimulation of the motor or the frontal cortex? Cortex J Devot Study Nerv Syst Behav 97:96–108. CrossRefGoogle Scholar
  73. Rawji V et al (2018) tDCS changes in motor excitability are specific to orientation of current flow. Brain Stimul 11:289–298. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Rothwell JC (2012) Clinical applications of noninvasive electrical stimulation: problems and potential. Clin EEG Neurosci 43:209–214. CrossRefPubMedGoogle Scholar
  75. Rudroff T, Kindred JH, Ketelhut NB (2016) Fatigue in multiple sclerosis: misconceptions and future research directions. Front Neurol 7:122. CrossRefPubMedPubMedCentralGoogle Scholar
  76. Saenz A et al (2010) Knee isokinetic test-retest: a multicentre knee isokinetic test-retest study of a fatigue protocol. Eur J Phys Rehabilit Med 46:81–88Google Scholar
  77. Sales MM, De Sousa CV, Browne RAV, Fontes EB, Olher RDRV, Ernesto C, Simões HG (2016) Transcranial direct current stimulation improves muscle isokinetic performance of young trained individuals. Med Sport 69:163–172Google Scholar
  78. Sanchez-Kuhn A, Perez-Fernandez C, Canovas R, Flores P, Sanchez-Santed F (2017) Transcranial direct current stimulation as a motor neurorehabilitation tool: an empirical review. Biomed Eng Online 16:76. CrossRefPubMedPubMedCentralGoogle Scholar
  79. Schambra HM, Abe M, Luckenbaugh DA, Reis J, Krakauer JW, Cohen LG (2011) Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study. J Neurophysiol 106:652–661. CrossRefPubMedPubMedCentralGoogle Scholar
  80. Sliwowski R, Grygorowicz M, Wieczorek A, Jadczak L (2018) The relationship between jumping performance, isokinetic strength and dynamic postural control in elite youth soccer players. J Sports Med Phys Fit 58:1226–1233. CrossRefGoogle Scholar
  81. Stagg CJ, Jayaram G, Pastor D, Kincses ZT, Matthews PM, Johansen-Berg H (2011) Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning. Neuropsychologia 49:800–804. CrossRefPubMedPubMedCentralGoogle Scholar
  82. Stagg CJ, Lin RL, Mezue M, Segerdahl A, Kong Y, Xie J, Tracey I (2013) Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex. J Neurosci 33:11425–11431. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Stephens JA, Jones KT, Berryhill ME (2017) Task demands, tDCS intensity, and the COMT val(158)met polymorphism impact tDCS-linked working memory training gains. Sci Rep 7:13463. CrossRefPubMedPubMedCentralGoogle Scholar
  84. Tecchio F et al (2014) Multiple sclerosis fatigue relief by bilateral somatosensory cortex neuromodulation. J Neurol 261:1552–1558. CrossRefPubMedGoogle Scholar
  85. Thorstensson A, Karlsson J (1976) Fatiguability and fibre composition of human skeletal muscle. Acta Physiol Scand 98:318–322. CrossRefPubMedGoogle Scholar
  86. Trapp NT, Xiong W, Gott BM, Espejo GD, Bikson M, Conway CR (2019) Proceedings# 51: 4 mA adaptive transcranial direct current stimulation for treatment-resistant depression: early demonstration of feasibility with a 20-session course. Brain Stimulat Basic Transl Clin Res Neuromodul 12:e124–e125CrossRefGoogle Scholar
  87. Vitor-Costa M, Okuno NM, Bortolotti H, Bertollo M, Boggio PS, Fregni F, Altimari LR (2015) Improving cycling performance: transcranial direct current stimulation increases time to exhaustion in cycling. PLoS ONE 10:e0144916. CrossRefPubMedPubMedCentralGoogle Scholar
  88. Williams PS, Hoffman RL, Clark BC (2013) Preliminary evidence that anodal transcranial direct current stimulation enhances time to task failure of a sustained submaximal contraction. PLoS ONE 8:e81418. CrossRefPubMedPubMedCentralGoogle Scholar
  89. Ziemann U, Siebner HR (2008) Modifying motor learning through gating and homeostatic metaplasticity. Brain Stimulat 1:60–66. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Craig D. Workman
    • 1
  • John Kamholz
    • 2
  • Thorsten Rudroff
    • 1
    • 2
    Email author
  1. 1.Department of Health and Human PhysiologyUniversity of IowaIowa CityUSA
  2. 2.Department of NeurologyUniversity of Iowa Hospitals and ClinicsIowa CityUSA

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