Targeting the Human Cerebellum with Transcranial Direct Current Stimulation to Modulate Behavior: a Meta-Analysis

Viola Oldrati, Dennis J L G Schutter, Viola Oldrati, Dennis J L G Schutter

Abstract

Transcranial direct current stimulation (tDCS) is increasingly used to study motor- and non-motor-related functions of the cerebellum. The aim of the present study was to quantitatively review available studies to estimate the efficacy of cerebellar tDCS in altering motor- and cognitive-related behavioral performance in healthy volunteers. The present meta-analysis included 32 sham-controlled studies. Results from random effects modeling of the cumulative effect size demonstrated that anodal and cathodal tDCS to the cerebellum were effective in changing performance. No evidence for polarity-dependent effects of cerebellar tDCS was found. Current findings establish the feasibility to target motor and non-motor-related cerebellar functions with tDCS, but arguably due to anatomical differences between the cerebellum and cerebral cortex, the polarity of tDCS is not predictive of the direction of the behavioral changes in healthy volunteers.

Keywords: Cerebellum; Cognition; Meta-analysis; Motor; Performance; Transcranial direct current stimulation.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart study selection procedure
Fig. 2
Fig. 2
Forest plot showing effect size estimates (Hedges’ d) and 95% confidence interval of the experiments comparing anodal with sham cDCS in healthy volunteers
Fig. 3
Fig. 3
Forest plot showing absolute cumulative effect size estimates (Hedges’ d) and 95% confidence interval of the experiments comparing cathodal with sham cDCS in healthy volunteers

References

    1. Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000;527:633–639. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
    1. Filmer HL, Dux PE, Mattingley JB. Applications of transcranial direct current stimulation for understanding brain function. Trends Neurosci. 2014;37:742–753. doi: 10.1016/j.tins.2014.08.003.
    1. Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transcranial direct current stimulation: state of the art 2008. Brain Stimul. 2008;1:206–223. doi: 10.1016/j.brs.2008.06.004.
    1. Shin YI, Foerster Á, Nitsche MA. Transcranial direct current stimulation (tDCS)—application in neuropsychology. Neuropsychologia. 2015;69:154–175. doi: 10.1016/j.neuropsychologia.2015.02.002.
    1. van Dun K, Bodranghien F, Manto M, Mariën P. Targeting the cerebellum by noninvasive neurostimulation: a review. Cerebellum. 2017;16:695–741. doi: 10.1007/s12311-016-0840-7.
    1. Ugawa Y, Rothwell JC, Day BL, Thompson PD, Marsden CD. Percutaneous electrical stimulation of corticospinal pathways at the level of the pyramidal decussation in humans. Ann Neurol. 1991;29:418–427. doi: 10.1002/ana.410290413.
    1. Ugawa Y, Day BL, Rothwell JC, Thompson PD, Merton PA, Marsden CD. Modulation of motor cortical excitability by electrical stimulation over the cerebellum in man. J Physiol. 1991;441:57–72. doi: 10.1113/jphysiol.1991.sp018738.
    1. Galea JM, Jayaram G, Ajagbe L, Celnik P. Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation. J Neurosci. 2009;29:9115–9122. doi: 10.1523/JNEUROSCI.2184-09.2009.
    1. Hamada M, Strigaro G, Murase N, Sadnicka A, Galea JM, Edwards MJ, et al. Cerebellar modulation of human associative plasticity. J Physiol. 2012;590:2365–2374. doi: 10.1113/jphysiol.2012.230540.
    1. Parazzini M, Rossi E, Ferrucci R, Liorni I, Priori A, Ravazzani P. Modelling the electric field and the current density generated by cerebellar transcranial DC stimulation in humans. Clin Neurophysiol. 2014;125:577–584. doi: 10.1016/j.clinph.2013.09.039.
    1. Tremblay S, Austin D, Hannah R, Rothwell JC. Non-invasive brain stimulation as a tool to study cerebellar-M1 interactions in humans. Cerebellum Ataxias. 2016;3:19. doi: 10.1186/s40673-016-0057-z.
    1. Van Dun K, Bodranghien F, Mariën P, Manto M. TDCS of the cerebellum: where do we stand in 2016? Technical issues and critical review of the literature Front Hum Neurosci. 2016;11:199.
    1. Priori A, Ciocca M, Parazzini M, Vergari M, Ferrucci R. Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists. J Physiol. 2014;592:3345–3369. doi: 10.1113/jphysiol.2013.270280.
    1. Avila E, Van Der Geest JN, Kengne Kamga S, Verhage MC, Donchin O, Frens MA. Cerebellar transcranial direct current stimulation effects on saccade adaptation. Neural Plast. 2015;2015:968970. doi: 10.1155/2015/968970.
    1. Beyer L, Batsikadze G, Timmann D, Gerwig M. Cerebellar tDCS effects on conditioned eyeblinks using different electrode placements and stimulation protocols. Front Hum Neurosci. 2017;11:23. doi: 10.3389/fnhum.2017.00023.
    1. Boehringer A, Macher K, Dukart J, Villringer A, Pleger B. Cerebellar transcranial direct current stimulation modulates verbal working memory. Brain Stimul. 2013;6:649–653. doi: 10.1016/j.brs.2012.10.001.
    1. Cantarero G, Spampinato D, Reis J, Ajagbe L, Thompson T, Kulkarni K, et al. Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy. J Neurosci. 2015;35:3285–3290. doi: 10.1523/JNEUROSCI.2885-14.2015.
    1. Craig CE, Doumas M. Anodal transcranial direct current stimulation shows minimal, measure-specific effects on dynamic postural control in young and older adults: a double blind, sham-controlled study. PLoS One. 2017;12:e0170331. doi: 10.1371/journal.pone.0170331.
    1. D'Mello AM, Turkeltaub PE, Stoodley CJ. Cerebellar tDCS modulates neural circuits during semantic prediction: a combined tDCS-fMRI study. J Neurosci. 2017;37:1604–1613. doi: 10.1523/JNEUROSCI.2818-16.2017.
    1. Doppelmayr M, Pixa NH, Steinberg F. Cerebellar, but not motor or parietal, high-density anodal transcranial direct current stimulation facilitates motor adaptation. J Int Neuropsychol Soc. 2016;22:1–9. doi: 10.1017/S1355617716000345.
    1. Ehsani F, Bakhtiary AH, Jaberzadeh S, Talimkhani A, Hajihasani A. Differential effects of primary motor cortex and cerebellar transcranial direct current stimulation on motor learning in healthy individuals: a randomized double-blind sham-controlled study. Neurosci Res. 2016;112:10–19. doi: 10.1016/j.neures.2016.06.003.
    1. Fernandez L, Albein-Urios N, Kirkovski M, McGinley JL, Murphy AT, Hyde C, et al. Cathodal transcranial direct current stimulation (tDCS) to the right cerebellar hemisphere affects motor adaptation during gait. Cerebellum. 2016;16:168–177. doi: 10.1007/s12311-016-0788-7.
    1. Ferrucci R, Giannicola G, Rosa M, Fumagalli M, Boggio PS, Hallett M, et al. Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness. Cogn Emot. 2012;26:786–799. doi: 10.1080/02699931.2011.619520.
    1. Ferrucci R, Brunoni AR, Parazzini M, Vergari M, Rossi E, Fumagalli M, et al. Modulating human procedural learning by cerebellar transcranial direct current stimulation. Cerebellum. 2013;12:485–492. doi: 10.1007/s12311-012-0436-9.
    1. Galea JM, Vazquez A, Pasricha N, Orban De Xivry JJ, Celnik P. Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. Cereb Cortex. 2011;21:1761–1770. doi: 10.1093/cercor/bhq246.
    1. Hardwick RM, Celnik P. Cerebellar direct current stimulation enhances motor learning in older adults. Neurobiol Aging. 2014;35:2217–2221. doi: 10.1016/j.neurobiolaging.2014.03.030.
    1. Inukai Y, Saito K, Sasaki R, Kotan S, Nakagawa M, Onishi H. Influence of transcranial direct current stimulation to the cerebellum on standing posture control. Front Hum Neurosci. 2016;10:325.
    1. Jalali R, Miall RC, Galea JM. No consistent effect of cerebellar transcranial direct current stimulation (tDCS) on visuomotor adaptation. J Neurophysiol. 2017. doi:10.1152/jn.00896.2016.
    1. Lametti DR, Oostwoud Wijdenes L, Bonaiuto J, Bestmann S, Rothwell JC. Cerebellar tDCS dissociates the timing of perceptual decisions from perceptual change in speech. J Neurophysiol. 2016;116:2023–2032. doi: 10.1152/jn.00433.2016.
    1. Macher K, Bohringer A, Villringer A, Pleger B. Cerebellar-parietal connections underpin phonological storage. J Neurosci. 2014;34:5029–5037. doi: 10.1523/JNEUROSCI.0106-14.2014.
    1. Majidi N, Verhage MC, Donchin O, Holland P, Frens MA, van der Geest JN. Cerebellar tDCS does not improve performance in probabilistic classification learning. Exp Brain Res. 2016;235:421–428. doi: 10.1007/s00221-016-4800-8.
    1. Miall RC, Antony J, Goldsmith-Sumner A, Harding SR, McGovern C, Winter JL. Modulation of linguistic prediction by tDCS of the right lateral cerebellum. Neuropsychologia. 2016;86:103–109. doi: 10.1016/j.neuropsychologia.2016.04.022.
    1. Panico F, Sagliano L, Grossi D, Trojano L. Cerebellar cathodal tDCS interferes with recalibration and spatial realignment during prism adaptation procedure in healthy subjects. Brain Cogn. 2016;105:1–8. doi: 10.1016/j.bandc.2016.03.002.
    1. Picazio S, Granata C, Caltagirone C, Petrosini L, Oliveri M. Shaping pseudoneglect with transcranial cerebellar direct current stimulation and music listening. Front Hum Neurosci. 2015;9:1–9. doi: 10.3389/fnhum.2015.00158.
    1. Pope P, Miall RC. Task-specific facilitation of cognition by cathodal transcranial direct current stimulation of the cerebellum. Brain Stimul. 2012;5:84–94. doi: 10.1016/j.brs.2012.03.006.
    1. Shah B, Nguyen TT, Madhavan S. Polarity independent effects of cerebellar tDCS on short term ankle visuomotor learning. Brain Stimul. 2013;6:966–968. doi: 10.1016/j.brs.2013.04.008.
    1. Shimizu RE, Wu AD, Samra JK, Knowlton BJ. The impact of cerebellar transcranial direct current stimulations (tDCS) on learning fine-motor sequences. Philos Trans R Soc Lond Ser B Biol Sci. 2017;372:20160050. doi: 10.1098/rstb.2016.0050.
    1. Spielmann K, van der Vliet R, van de Sandt-Koenderman WM, Frens MA, Ribbers GM, Selles RW, van Vugt S, van der Geest JN, Holland P. Cerebellar cathodal transcranial direct stimulation and performance on a verb generation task: a replication study. Neural Plast. 2017;2017:1254615. doi: 10.1155/2017/1254615.
    1. Steiner KM, Enders A, Thier W, Batsikadze G, Ludolph N, Ilg W, et al. Cerebellar tDCS does not improve learning in a complex whole body dynamic balance task in young healthy subjects. PLoS One. 2016;11:e0163598. doi: 10.1371/journal.pone.0163598.
    1. Taubert M, Stein T, Kreutzberg T, Stockinger C, Hecker L, Focke A, et al. Remote effects of non-invasive cerebellar stimulation on error processing in motor re-learning. Brain Stimul. 2015;9:692–699. doi: 10.1016/j.brs.2016.04.007.
    1. Van Wessel BW, Claire Verhage M, Holland P, Frens MA, van der Geest JN. Cerebellar tDCS does not affect performance in the N-back task. J Clin Exp Neuropsychol. 2015:38319–26.
    1. Verhage MC, Avila EO, Frens MA, Donchin O, van der Geest JN. Cerebellar tDCS does not enhance performance in an implicit categorization learning task. Front Psychol. 2017;8:476. doi: 10.3389/fpsyg.2017.00476.
    1. Yavari F, Mahdavi S, Towhidkhah F, Ahmadi-Pajouh MA, Ekhtiari H, Darainy M. Cerebellum as a forward but not inverse model in visuomotor adaptation task: a tDCS-based and modeling study. Exp Brain Res. 2016;234:997–1012. doi: 10.1007/s00221-015-4523-2.
    1. Zuchowski ML, Timmann D, Gerwig M. Acquisition of conditioned eyeblink responses is modulated by cerebellar tDCS. Brain Stimul. 2014;7:525–531. doi: 10.1016/j.brs.2014.03.010.
    1. Samaei A, Ehsani F, Zoghi M, Hafez Yosephi M, Jaberzadeh S. Online and offline effects of cerebellar transcranial direct current stimulation on motor learning in healthy older adults: a randomized double-blind sham-controlled study. Eur J Neurosci. 2017;45:1177–1185. doi: 10.1111/ejn.13559.
    1. Hedges LV, Olkin I. Statistical methods for meta-analysis. 1. London: Academic Press; 1985.
    1. Hedges LV. Distribution theory for Glass’s estimator of effect size and related estimators. J Educ Stat. 1981;6:107. doi: 10.3102/10769986006002107.
    1. Borenstein M, Higgins JP, Hedges LV, Rothstein HR. Basics of meta-analysis: I2 is not an absolute measure of heterogeneity. Res Synth Methods. 2017;8:5–18. doi: 10.1002/jrsm.1230.
    1. Rosenberg MS, Adams DC, Gurevitch J. MetaWin: statistical software for meta-analysis version 2. Sunderland, Massachusetts: Sinauer Associates; 2000.
    1. Lipsey MW, Wilson DB. Practical meta-analysis. 1ste. London: Sage Publications; 2001.
    1. Rampersad SM, Janssen AM, Lucka F, Aydin Ü, Lanfer B, Lew S, et al. Simulating transcranial direct current stimulation with a detailed anisotropic human head model. IEEE Trans Neural Syst Rehabil Eng. 2014;22:441–452. doi: 10.1109/TNSRE.2014.2308997.
    1. Middleton FA, Strick PL. Cerebellar projections to the prefrontal cortex of the primate. J Neurosci. 2001;21:700–712.
    1. Ramnani N. The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci. 2006;7:511–522. doi: 10.1038/nrn1953.
    1. Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2010;46:831–844. doi: 10.1016/j.cortex.2009.11.008.
    1. Koziol LF, Budding D, Andreasen N, D’Arrigo S, Bulgheroni S, Imamizu H, et al. Consensus paper: the cerebellum’s role in movement and cognition. Cerebellum. 2014;13:151–177. doi: 10.1007/s12311-013-0511-x.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera