Compromised tDCS-induced facilitation of motor consolidation in patients with multiple sclerosis
To investigate whether consolidation after motor learning can be facilitated by offline (post-training) transcranial direct current stimulation (tDCS) in patients with multiple sclerosis (MS).
In this cross-sectional double-blind interventional study, effects of tDCS on motor consolidation were examined in 14 patients with relapsing remitting MS [median Expanded Disability Status Scale score 2.0 (range 1–4)] and 14 age- and sex-matched healthy controls. tDCS with the anode placed over the left primary motor cortex and the cathode placed over the right supraorbital region was applied immediately after a training session of an explicit sequential finger-tapping task that was performed with the right (dominant) hand. Task performance was retested after an interval of 8 h to assess consolidation. Participants took part in two experimental sessions separated by at least 7 days which differed with respect to type of post-training tDCS, i.e., sham and verum stimulation.
Patients with MS performed worse than controls in functional motor tests and the motor sequence task. However, learning speed and magnitude of online performance increments during the training session were comparable to controls. While post-training tDCS facilitated motor consolidation in controls, patients with MS did not benefit from this type of intervention.
Absence of post-training tDCS-induced facilitation of consolidation in patients with MS suggests that the interaction of tDCS with the motor consolidation network is inefficient. Identification of the underlying disease-related mechanisms will have important implications for the design of studies aiming to promote motor recovery in MS by non-invasive brain stimulation.
KeywordsMotor learning Motor consolidation Multiple sclerosis Transcranial direct current stimulation
J-JR: designed and conceptualized study; analyzed the data; interpreted the data; drafted the manuscript for intellectual content. SD: major role in the acquisition of data; revised the manuscript for intellectual content. MS: designed and conceptualized study; revised the manuscript for intellectual content. CF: analyzed the data; revised the manuscript for intellectual content. DW: revised the manuscript for intellectual content. FTB: revised the manuscript for intellectual content. JC: designed and conceptualized study; revised the manuscript for intellectual content.
No industry, government or institutional funding was received for this research.
Compliance with ethical standards
Conflict of interest
All authors declare no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work, and no other relationships or activities that could appear to have influenced the submitted work.
Ethics approval was provided by the institutional ethical standards committee on human experimentation at the University of Leipzig (371/14-ek). All participants provided written informed consent before the conduct of any study-related procedures.
- 4.Zeller D, Classen J (2014) Plasticity of the Motor System in Multiple Sclerosis. Neuroscience 283:222–230. https://doi.org/10.1016/j.neuroscience.2014.05.043 CrossRefPubMedGoogle Scholar
- 13.Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol Lond 527(3):633–639. https://doi.org/10.1111/j.1469-7793.2000.t01-1-00633.x CrossRefPubMedCentralPubMedGoogle Scholar
- 14.Buch ER, Santarnecchi E, Antal A, Born J, Celnik PA, Classen J, Gerloff C, Hallett M, Hummel FC, Nitsche MA, Pascual-Leone A, Paulus WJ, Reis J, Robertson EM, Rothwell JC, Sandrini M, Schambra HM, Wassermann EM, Ziemann U, Cohen LG (2017) Effects of tDCS on motor learning and memory formation: a consensus and critical position paper. Clin Neurophysiol 128(4):589–603. https://doi.org/10.1016/j.clinph.2017.01.004 CrossRefPubMedGoogle Scholar
- 15.Antal A, Nitsche MA, Kincses TZ, Kruse W, Hoffmann KP, Paulus W (2004) Facilitation of visuo-motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans. Eur J Neurosci 19(10):2888–2892. https://doi.org/10.1111/j.1460-9568.2004.03367.x CrossRefPubMedGoogle Scholar
- 16.Hummel FC, Heise K, Celnik P, Floel A, Gerloff C, Cohen LG (2010) Facilitating skilled right hand motor function in older subjects by anodal polarization over the left primary motor cortex. Neurobiol Aging 31(12):2160–2168. https://doi.org/10.1016/j.neurobiolaging.2008.12.008 CrossRefPubMedGoogle Scholar
- 18.Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, Tergau F (2003) Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci 15(4):619–626. https://doi.org/10.1162/089892903321662994 CrossRefPubMedGoogle Scholar
- 19.Hamoudi M, Schambra HM, Fritsch B, Schoechlin-Marx A, Weiller C, Cohen LG, Reis J (2018) Transcranial direct current stimulation enhances motor skill learning but not generalization in chronic stroke. Neurorehabil Neural Repair. https://doi.org/10.1177/1545968318769164 (1545968318769164) CrossRefPubMedGoogle Scholar
- 20.Reis J, Schambra HM, Cohen LG, Buch ER, Fritsch B, Zarahn E, Celnik PA, Krakauer JW (2009) Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc Natl Acad Sci USA 106(5):1590–1595. https://doi.org/10.1073/pnas.0805413106 CrossRefGoogle Scholar
- 23.Krause V, Meier A, Dinkelbach L, Pollok B (2016) Beta band transcranial alternating (tACS) and direct current stimulation (tDCS) applied after initial learning facilitate retrieval of a motor sequence. Front Behav Neurosci. https://doi.org/10.3389/fnbeh.2016.00004 CrossRefPubMedCentralPubMedGoogle Scholar
- 24.Rumpf JJ, Wegscheider M, Hinselmann K, Fricke C, King BR, Weise D, Klann J, Binkofski F, Buccino G, Karni A, Doyon J, Classen J (2017) Enhancement of motor consolidation by post-training transcranial direct current stimulation in older people. Neurobiol Aging 49:1–8. https://doi.org/10.1016/j.neurobiolaging.2016.09.003 CrossRefPubMedGoogle Scholar
- 28.Smith A (1968) The symbol-digit modalities test: a neuropsychologic test of learning and other cerebral disorders. In: Helmuth J (ed) Learning disorders. Special Child Publications, Seattle, pp 83–91Google Scholar
- 29.Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O’Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302. https://doi.org/10.1002/ana.22366 CrossRefPubMedCentralPubMedGoogle Scholar
- 34.King BR, Saucier P, Albouy G, Fogel SM, Rumpf JJ, Klann J, Buccino G, Binkofski F, Classen J, Karni A, Doyon J (2017) Cerebral activation during initial motor learning forecasts subsequent sleep-facilitated memory consolidation in older adults. Cereb Cortex 27(2):1588–1601. https://doi.org/10.1093/cercor/bhv347 CrossRefPubMedGoogle Scholar
- 37.Mancini L, Ciccarelli O, Manfredonia F, Thornton JS, Agosta F, Barkhof F, Beckmann C, De Stefano N, Enzinger C, Fazekas F, Filippi M, Gass A, Hirsch JG, Johansen-Berg H, Kappos L, Korteweg T, Manson SC, Marino S, Matthews PM, Montalban X, Palace J, Polman C, Rocca M, Ropele S, Rovira A, Wegner C, Friston K, Thompson A, Yousry T (2009) Short-term adaptation to a simple motor task: a physiological process preserved in multiple sclerosis. Neuroimage 45(2):500–511. https://doi.org/10.1016/j.neuroimage.2008.12.006 CrossRefPubMedGoogle Scholar
- 38.Bonzano L, Tacchino A, Roccatagliata L, Sormani MP, Mancardi GL, Bove M (2011) Impairment in explicit visuomotor sequence learning is related to loss of microstructural integrity of the corpus callosum in multiple sclerosis patients with minimal disability. Neuroimage 57(2):495–501. https://doi.org/10.1016/j.neuroimage.2011.04.037 CrossRefPubMedGoogle Scholar
- 42.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(5):800–804. https://doi.org/10.1016/j.neuropsychologia.2011.02.009 CrossRefPubMedCentralPubMedGoogle Scholar
- 46.Albouy G, Sterpenich V, Balteau E, Vandewalle G, Desseilles M, Dang-Vu T, Darsaud A, Ruby P, Luppi PH, Degueldre C, Peigneux P, Luxen A, Maquet P (2008) Both the hippocampus and striatum are involved in consolidation of motor sequence memory. Neuron 58(2):261–272. https://doi.org/10.1016/j.neuron.2008.02.008 CrossRefPubMedGoogle Scholar
- 47.Debas K, Carrier J, Orban P, Barakat M, Lungu O, Vandewalle G, Hadj Tahar A, Bellec P, Karni A, Ungerleider LG, Benali H, Doyon J (2010) Brain plasticity related to the consolidation of motor sequence learning and motor adaptation. Proc Natl Acad Sci USA 107(41):17839–17844. https://doi.org/10.1073/pnas.1013176107 CrossRefPubMedGoogle Scholar
- 48.Debas K, Carrier J, Barakat M, Marrelec G, Bellec P, Hadj Tahar A, Karni A, Ungerleider LG, Benali H, Doyon J (2014) Off-line consolidation of motor sequence learning results in greater integration within a cortico-striatal functional network. Neuroimage 99:50–58. https://doi.org/10.1016/j.neuroimage.2014.05.022 CrossRefPubMedGoogle Scholar
- 49.Krause MR, Zanos TP, Csorba BA, Pilly PK, Choe J, Phillips ME, Datta A, Pack CC (2017) Transcranial direct current stimulation facilitates associative learning and alters functional connectivity in the primate brain. Curr Biol 27(20):3086–3096 e3083. https://doi.org/10.1016/j.cub.2017.09.020 CrossRefPubMedGoogle Scholar