Effects of High-Definition and Conventional Transcranial Direct-Current Stimulation on Motor Learning in Children

Lauran Cole, Adrianna Giuffre, Patrick Ciechanski, Helen L Carlson, Ephrem Zewdie, Hsing-Ching Kuo, Adam Kirton, Lauran Cole, Adrianna Giuffre, Patrick Ciechanski, Helen L Carlson, Ephrem Zewdie, Hsing-Ching Kuo, Adam Kirton

Abstract

Background: Transcranial direct current stimulation (tDCS) can improve motor learning in children. High-definition approaches (HD-tDCS) have not been examined in children. Objectives/Hypothesis: We hypothesized that primary motor cortex HD-tDCS would enhance motor learning but be inferior to tDCS in children. Methods: Twenty-four children were recruited for a randomized, sham-controlled, double-blinded interventional trial (NCT03193580, clinicaltrials.gov/ct2/show/NCT03193580) to receive (1) right hemisphere (contralateral) primary motor cortex (M1) 1 mA anodal conventional 1 × 1 tDCS (tDCS), (2) right M1 1 mA anodal 4 × 1 HD-tDCS (HD-tDCS), or (3) sham. Over five consecutive days, participants trained their left hand using the Purdue Pegboard Test (PPTL). The Jebsen-Taylor Test, Serial Reaction Time Task, and right hand and bimanual PPT were also tested at baseline, post-training, and 6-week retention time (RT). Results: Both the tDCS and HD-tDCS groups demonstrated enhanced motor learning compared to sham with effects maintained at 6 weeks. Effect sizes were moderate-to-large for tDCS and HD-tDCS groups at the end of day 4 (Cohen's d tDCS = 0.960, HD-tDCS = 0.766) and day 5 (tDCS = 0.655, HD-tDCS = 0.851). Enhanced motor learning effects were also seen in the untrained hand. HD-tDCS was well tolerated and safe with no adverse effects. Conclusion: HD-tDCS and tDCS can enhance motor learning in children. Further exploration is indicated to advance rehabilitation therapies for children with motor disabilities such as cerebral palsy. Clinical Trial Registration: clinicaltrials.gov, identifier NCT03193580.

Keywords: HD-tDCS; child; developmental neuroplasticity; motor learning; non-invasive brain stimulation; tDCS.

Figures

FIGURE 1
FIGURE 1
Accelerated motor learning in pediatrics (AMPED) protocol. (A) Participants received an MRI, complete tasks in a virtual reality KINARM robotic system, received TMS motor mapping (TMSMM), completed a series of motor assessments and then received training paired with non-invasive brain stimulation interventions. On days 2–4, subjects perform the PPT during intervention. Participants repeat the Day 1 tasks on Day 5 (with training) and at a 6-weeks retention testing follow up (RT). (B) PPT training is paired with stimulation by treatment groups with electrode montages (C) shown for tDCS (left) and HD-tDCS (right) where dark gray electrodes are anodes and light gray electrodes are cathodes. Black arrows represent the direction of current flow from anode to cathode(s).
FIGURE 2
FIGURE 2
Motor learning by treatment group. (A) The mean daily change from baseline (B) in left Purdue Pegboard (PPTL) learning curves for sham (white triangles) were lower than both tDCS (gray circles) and HD-tDCS (black circles). Effects decayed by 6 weeks retention time (RT) for sham but not tDCS groups. (B) Daily mean scores per repetition of the PPTL are shown for the same three groups. ∗p < 0.05 for tDCS vs. sham, #p < 0.05 for HD-tDCS vs. sham.
FIGURE 3
FIGURE 3
Online and offline learning effects on left hand Purdue Pegboard (PPTL) for the three intervention groups. The online effects represent the difference in PPTL score from the first and last training point of the day. The offline learning represents the difference between the last training time point of the day to the first training point of the following day. ∗p < 0.05, ∗∗p < 0.01.
FIGURE 4
FIGURE 4
Effect of performance status on motor learning enhancement. (A) Low performers (baseline PPTL below the median score) demonstrated marked separation of PPTL learning curves with tDCS (gray circles) and HD-tDCS (black circles) outperforming sham (white triangles). (B) Treatment group effects were not observed for high performers. B refers to baseline. ∗p < 0.05 for sham vs. tDCS, #p < 0.05 for sham vs. HD-tDCS.
FIGURE 5
FIGURE 5
Secondary motor outcomes. (A) Change in Purdue Pegboard Test (PPT) scores at post-training and retention time (RT) demonstrated treatment group effects for PPTA. PPT subtests are left (PPTL), right (PPTR), bimanual (PPTLR), sum of scores (PPTS), and assembly (PPTA). ∗p < 0.05. (B) Jebsen–Taylor Test of Hand Function left and right (JTTL, JTTR) demonstrated treatment group effects bilaterally at post-training and RT. (C) Serial Reaction Time Task (SRTT) curves with and without <200 ms responses are shown. Blocks 1 and 6 are random while all others follow a 12-character sequence. (D) SRTT by intervention group with <200 ms responses excluded.
FIGURE 6
FIGURE 6
Combined PPTL training data for sham and tDCS groups over 3 days. (A) Sham (white triangles, n = 14) learning curves were inferior to both tDCS (gray circles, n = 14) and HD-tDCS (black circles, n = 8) groups. (B) Mean daily learning for the same three groups form the combined studies. Both the tDCS and HD-tDCS groups placed more pegs each day as compared to sham.

References

    1. Alam M., Bikson M., Truong D. (2014). Spatial and polarity precision of high-definition transcranial direct current stimulation (HD-tDCS). Brain Stimulat. 7:e11. 10.1016/j.brs.2014.01.039
    1. Ambrus G. G., Al-Moyed H., Chaieb L., Sarp L., Antal A., Paulus W. (2012). The fade-in – Short stimulation – Fade out approach to sham tDCS – Reliable at 1 mA for naïve and experienced subjects, but not investigators. Brain Stimulat. 5 499–504. 10.1016/j.brs.2011.12.001
    1. Anguera J. A., Russell C. A., Noll D. C., Seidler R. D. (2007). Neural correlates associated with intermanual transfer of sensorimotor adaptation. Brain Res. 1185 136–151. 10.1016/j.brainres.2007.09.088
    1. Antal A., Kincses T. Z., Nitsche M. A., Paulus W. (2003). Manipulation of phosphene thresholds by transcranial direct current stimulation in man. Exp. Brain Res. 150 375–378. 10.1007/s00221-003-1459-8
    1. Biabani M., Aminitehrani M., Zoghi M., Farrell M., Egan G., Jaberzadeh S. (2018). The effects of transcranial direct current stimulation on short-interval intracortical inhibition and intracortical facilitation: a systematic review and meta-analysis. Rev. Neurosci. 29 99–114. 10.1515/revneuro-2017-0023
    1. Bikson M., Grossman P., Thomas C., Zannou A. L., Jiang J., Adnan T., et al. (2016). Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimulat. 9 641–661. 10.1016/j.brs.2016.06.004
    1. Bindman L. J., Lippold O. C., Redfearn J. W. (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. 10.1113/jphysiol.1964.sp007425
    1. Boggio P. S., Castro L. O., Savagim E. A., Braite R., Cruz V. C., Rocha R. R., et al. (2006). Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation. Neurosci. Lett. 404 232–236. 10.1016/j.neulet.2006.05.051
    1. Brain Development Cooperative Group. (2012). Total and regional brain volumes in a population-based normative sample from 4 to 18 years: the NIH MRI study of normal brain development. Cereb. Cortex 22 1–12. 10.1093/cercor/bhr018
    1. Caparelli-Daquer E. M., Zimmermann T. J., Mooshagian E., Parra L. C., Rice J. K., Datta A., et al. (2012). A pilot study on effects of 4 × 1 high-definition tDCS on motor cortex excitability. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2012 735–738. 10.1109/EMBC.2012.6346036
    1. Ciechanski P., Carlson H. L., Yu S. S., Kirton A. (2018). Modeling transcranial direct-current stimulation-induced electric fields in children and adults. Front. Hum. Neurosci. 12:268. 10.3389/fnhum.2018.00268
    1. Ciechanski P., Cheng A., Lopushinsky S., Hecker K., Gan L. S., Lang S., et al. (2017). Effects of transcranial direct-current stimulation on neurosurgical skill acquisition: a randomized controlled trial. World Neurosurg. 108 876.e4–884.e4. 10.1016/j.wneu.2017.08.123
    1. Ciechanski P., Kirton A. (2016). Transcranial direct-current stimulation can enhance motor learning in children. Cereb. Cortex 27 2758–2767. 10.1093/cercor/bhw114
    1. Datta A., Bansal V., Diaz J., Patel J., Reato D., Bikson M. (2009). Gyri –precise head model of transcranial DC stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimulat. 2 201–207. 10.1016/j.brs.2009.03.005
    1. Dayan E., Censor N., Buch E. R., Sandrini M., Cohen L. G. (2013). Noninvasive brain stimulation: from physiology to network dynamics and back. Nat. Neurosci. 16 838–844. 10.1038/nn.3422
    1. Dmochowski J. P., Datta A., Bikson M., Su Y., Parra L. C. (2011). Optimized multi-electrode stimulation increases focality and intensity at target. J. Neural Eng. 8:046011. 10.1088/1741-2560/8/4/046011
    1. Doppelmayr M., Pixa N. H., Steinberg F. (2016). Cerebellar, but not motor or parietal, high-density anodal transcranial direct current stimulation facilitates motor adaptation. J. Int. Neuropsychol. Soc. 22 928–936. 10.1017/S1355617716000345
    1. Dundas J. E., Thickbroom G. W., Mastaglia F. L. (2007). Perception of comfort during transcranial DC stimulation: effect of NaCl solution concentration applied to sponge electrodes. Clin. Neurophysiol. 118 1166–1170. 10.1016/j.clinph.2007.01.010
    1. Elizabeth Reedman S., Beagley S., Sakzewski L., Boyd R. N. (2015). The Jebsen taylor test of hand function: a pilot test-retest reliability study in typically developing children. Phys. Occup. Ther. Pediatr. 36 292–304. 10.3109/01942638.2015.1040576
    1. Elsner B., Kwakkel G., Kugler J., Mehrholz J. (2017). Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials. J. Neuroeng. Rehabil. 14:95. 10.1186/s12984-017-0301-7
    1. Fregni F., Pascual-Leone A. (2007). Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat. Clin. Pract. Neurol. 3 383–393. 10.1038/ncpneuro0530
    1. Fritsch B., Reis J., Martinowich K., Schambra H. M., Ji Y., Cohen L. G., et al. (2010). Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66 198–204. 10.1016/j.neuron.2010.03.035
    1. Galea M. P., Hammar I., Nilsson E., Jankowska E. (2010). Bilateral postsynaptic actions of pyramidal tract and reticulospinal neurons on feline erector spinae motoneurons. J. Neurosci. 30 858–869. 10.1523/JNEUROSCI.4859-09.2010
    1. Gardner R. A., Broman M. (1979). The purdue pegboard: normative data on 1334 school children. J. Clin. Child Psychol. 8 156–162. 10.1080/15374417909532912
    1. Garvey M. A., Kaczynski K. J., Becker D. A., Bartko J. J. (2001). Subjective reactions of children to single-pulse transcranial magnetic stimulation. J. Child Neurol. 16 891–894. 10.1177/088307380101601205
    1. Gillick B., Rich T., Nemanich S., Chen C.-Y., Menk J., Mueller B., et al. (2018). Transcranial direct current stimulation and constraint-induced therapy in cerebral palsy: a randomized, blinded, sham-controlled clinical trial. Eur. J. Paediatr. Neurol. 22 358–368. 10.1016/j.ejpn.2018.02.001
    1. Gillick B. T., Friel K. M., Menk J., Rudser K. (2016). “Therapeutic brain stimulation trials in children with cerebral palsy,” in Pediatric Brain Stimulation: Mapping and Modulating the Developing Brain, eds Kirton A., Gilbert D. L. (Amsterdam: Elsevier; ), 209–236.
    1. Gualtieri C. T., Johnson L. G. (2006). Reliability and validity of a computerized neurocognitive test battery, CNS vital signs. Arch. Clin. Neuropsychol. 21 623–643. 10.1016/j.acn.2006.05.007
    1. Hamoudi M., Schambra H. M., Fritsch B., Schoechlin-Marx A., Weiller C., Cohen L. G., et al. (2018). Transcranial direct current stimulation enhances motor skill learning but not generalization in chronic stroke. Neurorehabil. Neural Repair. 32 295–308. 10.1177/1545968318769164
    1. Honda M., Deiber M. P., Ibáñez V., Pascual-Leone A., Zhuang P., Hallett M. (1998). Dynamic cortical involvement in implicit and explicit motor sequence learning. A pet study. Brain J. Neurol. 121(Pt 11), 2159–2173. 10.1093/brain/121.11.2159
    1. Hummel F. C., Heise K., Celnik P., Floel A., Gerloff C., Cohen L. G. (2009). Facilitating skilled right hand motor function in older subjects by anodal polarization over the left primary motor cortex. Neurobiol. Aging 31 2160–2168. 10.1016/j.neurobiolaging.2008.12.008
    1. Kang N., Summers J. J., Cauraugh J. H. (2016). Transcranial direct current stimulation facilitates motor learning post-stroke: a systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 87 345–355. 10.1136/jnnp-2015-311242
    1. Kessler S. K., Minhas P., Woods A. J., Rosen A., Gorman C., Bikson M. (2013). Dosage considerations for transcranial direct current stimulation in children: a computational modeling study. PLoS One 8:e76112. 10.1371/journal.pone.0076112
    1. Kirton A. (2016). Advancing non-invasive neuromodulation clinical trials in children: Lessons from perinatal stroke. Eur. J. Paediatr. Neurol. 21 75–103. 10.1016/j.ejpn.2016.07.002
    1. Kirton A., Andersen J., Herrero M., Nettel-Aguirre A., Carsolio L., Damji O., et al. (2016). Brain stimulation and constraint for perinatal stroke hemiparesis: the plastic champs trial. Neurology 86 1659–1667. 10.1212/WNL.0000000000002646
    1. Kirton A., Ciechanski P., Zewdie E., Andersen J., Nettel-Aguirre A., Carlson H., et al. (2017). Transcranial direct current stimulation for children with perinatal stroke and hemiparesis. Neurology 88 259–267. 10.1212/WNL.0000000000003518
    1. Kuo H.-I., Bikson M., Datta A., Minhas P., Paulus W., Kuo M.-F., et al. (2013). Comparing cortical plasticity induced by conventional and high-definition 4 × 1 Ring tDCS: a neurophysiological study. Brain Stimulat. 6 644–648. 10.1016/j.brs.2012.09.010
    1. Lee H. J., Lim B. C., Hwang H., Hong J. S., Kim E. K., Kim H. S., et al. (2010a). Clinical presentations and neurodevelopmental outcomes of perinatal stroke in preterm and term neonates: a case series. J. Korean Med. Sci. 25 888–894. 10.3346/jkms.2010.25.6.888
    1. Lee M., Hinder M. R., Gandevia S. C., Carroll T. J. (2010b). The ipsilateral motor cortex contributes to cross-limb transfer of performance gains after ballistic motor practice. J. Physiol. 588 201–212. 10.1113/jphysiol.2009.183855
    1. Moliadze V., Schmanke T., Andreas S., Lyzhko E., Freitag C. M., Siniatchkin M. (2015). Stimulation intensities of transcranial direct current stimulation have to be adjusted in children and adolescents. Clin. Neurophysiol. 126 1392–1399. 10.1016/j.clinph.2014.10.142
    1. Nissen M. J., Bullemer P. (1987). Attentional requirements of learning: evidence from performance measures. Cogn. Psychol. 19 1–32. 10.1016/0010-0285(87)90002-8
    1. Nitsche M. A., Paulus W. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J. Physiol. 527(Pt 3), 633–639. 10.1111/j.1469-7793.2000.t01-1-00633.x
    1. Nitsche M. A., Paulus W. (2001). Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57 1899–1901. 10.1212/WNL.57.10.1899
    1. Nitsche M. A., Schauenburg A., Lang N., Liebetanz D., Exner C., Paulus W., et al. (2003). Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J. Cogn. Neurosci. 15 619–626. 10.1162/089892903321662994
    1. Nojima I., Mima T., Koganemaru S., Thabit M. N., Fukuyama H., Kawamata T. (2012). Human motor plasticity induced by mirror visual feedback. J. Neurosci. 32 1293–1300. 10.1523/JNEUROSCI.5364-11.2012
    1. Oskoui M., Coutinho F., Dykeman J., Jetté N., Pringsheim T. (2013). An update on the prevalence of cerebral palsy: a systematic review and meta-analysis. Dev. Med. Child Neurol. 55 509–519. 10.1111/dmcn.12080
    1. Pereira E. A. H., Raja K., Gangavalli R. (2011). Effect of training on interlimb transfer of dexterity skills in healthy adults. Am. J. Phys. Med. Rehabil. 90 25–34. 10.1097/PHM.0b013e3181fc7f6f
    1. Pixa N. H., Steinberg F., Doppelmayr M. (2017). High-definition transcranial direct current stimulation to both primary motor cortices improves unimanual and bimanual dexterity. Neurosci. Lett. 643 84–88. 10.1016/j.neulet.2017.02.033
    1. Prichard G., Weiller C., Fritsch B., Reis J. (2014). Effects of different electrical brain stimulation protocols on subcomponents of motor skill learning. Brain Stimulat. 7 532–540. 10.1016/j.brs.2014.04.005
    1. Reis J., Fritsch B. (2011). Modulation of motor performance and motor learning by transcranial direct current stimulation: Curr. Opin. Neurol. 24 590–596. 10.1097/WCO.0b013e32834c3db0
    1. Reis J., Robertson E. M., Krakauer J. W., Rothwell J., Marshall L., Gerloff C., et al. (2008). Consensus: can transcranial direct current stimulation and transcranial magnetic stimulation enhance motor learning and memory formation? Brain Stimul. 1 363–369. 10.1016/j.brs.2008.08.001
    1. Reis J., Schambra H. M., Cohen L. G., Buch E. R., Fritsch B., Zarahn E., et al. (2009). Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc. Natl. Acad. Sci. U.S.A. 106 1590–1595. 10.1073/pnas.0805413106
    1. Richardson J., Datta A., Dmochowski J., Parra L. C., Fridriksson J. (2015). Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. NeuroRehabilitation 36 115–126. 10.3233/NRE-141199
    1. Schambra H. M., Abe M., Luckenbaugh D. A., Reis J., Krakauer J. W., Cohen L. G. (2011). Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study. J. Neurophysiol. 106 652–661. 10.1152/jn.00210.2011
    1. Stagg C. J., Bachtiar V., Amadi U., Gudberg C. A., Ilie A. S., Sampaio-Baptista C., et al. (2014). Local GABA concentration is related to network-level resting functional connectivity. eLife 3:e01465. 10.7554/eLife.01465
    1. Stagg C. J., Bachtiar V., Johansen-Berg H. (2011). The role of GABA in human motor learning. Curr. Biol. 21 480–484. 10.1016/j.cub.2011.01.069
    1. Stagg C. J., Nitsche M. A. (2011). Physiological basis of transcranial direct current stimulation. Neuroscientist 17 37–53. 10.1177/1073858410386614
    1. Tecchio F., Zappasodi F., Assenza G., Tombini M., Vollaro S., Barbati G., et al. (2010). Anodal transcranial direct current stimulation enhances procedural consolidation. J. Neurophysiol. 104 1134–1140. 10.1152/jn.00661.2009
    1. Tiffin J., Asher E. J. (1948). The Purdue pegboard; norms and studies of reliability and validity. J. Appl. Psychol. 32 234–247. 10.1037/h0061266
    1. Villamar M. F., Volz M. S., Bikson M., Datta A., Dasilva A. F., Fregni F. (2013). Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS). J. Vis. Exp. 77:e50309. 10.3791/50309
    1. Vines B. W., Nair D. G., Schlaug G. (2006). Contralateral and ipsilateral motor effects after transcranial direct current stimulation. Neuroreport 17 671–674. 10.1097/00001756-200604240-00023
    1. von Rein E., Hoff M., Kaminski E., Sehm B., Steele C. J., Villringer A., et al. (2015). Improving motor performance without training: the effect of combining mirror visual feedback with transcranial direct current stimulation. J. Neurophysiol. 113 2383–2389. 10.1152/jn.00832.2014
    1. Zewdie E., Kirton A. (2016). “TMS basics: single and paired pulse neurophysiology,” in Pediatric Brain Stimulation: Mapping and Modulating the Developing Brain, eds Kirton A., Gilbert D. L. (Amsterdam: Elsevier; ).

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