Cortical priming strategies for gait training after stroke: a controlled, stratified trial

Sangeetha Madhavan, Brice T Cleland, Anjali Sivaramakrishnan, Sally Freels, Hyosok Lim, Fernando D Testai, Daniel M Corcos, Sangeetha Madhavan, Brice T Cleland, Anjali Sivaramakrishnan, Sally Freels, Hyosok Lim, Fernando D Testai, Daniel M Corcos

Abstract

Background: Stroke survivors experience chronic gait impairments, so rehabilitation has focused on restoring ambulatory capacity. High-intensity speed-based treadmill training (HISTT) is one form of walking rehabilitation that can improve walking, but its effectiveness has not been thoroughly investigated. Additionally, cortical priming with transcranial direct current stimulation (tDCS) and movement may enhance HISTT-induced improvements in walking, but there have been no systematic investigations. The objective of this study was to determine if motor priming can augment the effects of HISTT on walking in chronic stroke survivors.

Methods: Eighty-one chronic stroke survivors participated in a controlled trial with stratification into four groups: 1) control-15 min of rest (n = 20), 2) tDCS-15 min of stimulation-based priming with transcranial direct current stimulation (n = 21), 3) ankle motor tracking (AMT)-15 min of movement-based priming with targeted movements of the ankle and sham tDCS (n = 20), and 4) tDCS+AMT-15 min of concurrent tDCS and AMT (n = 20). Participants performed 12 sessions of HISTT (40 min/day, 3 days/week, 4 weeks). Primary outcome measure was walking speed. Secondary outcome measures included corticomotor excitability (CME). Outcomes were measured at pre, post, and 3-month follow-up assessments.

Results: HISTT improved walking speed for all groups, which was partially maintained 3 months after training. No significant difference in walking speed was seen between groups. The tDCS+AMT group demonstrated greater changes in CME than other groups. Individuals who demonstrated up-regulation of CME after tDCS increased walking speed more than down-regulators.

Conclusions: Our results support the effectiveness of HISTT to improve walking; however, motor priming did not lead to additional improvements. Upregulation of CME in the tDCS+AMT group supports a potential role for priming in enhancing neural plasticity. Greater changes in walking were seen in tDCS up-regulators, suggesting that responsiveness to tDCS might play an important role in determining the capacity to respond to priming and HISTT.

Trial registration: ClinicalTrials.gov , NCT03492229. Registered 10 April 2018 - retrospectively registered, https://ichgcp.net/clinical-trials-registry/NCT03492229 .

Keywords: High intensity; Locomotion; Motor priming; TMS; Treadmill training; tDCS.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flow diagram. Participant flow through the study included eligibility assessment, randomization, allocation, study completion, and inclusion in data analysis. Values in parentheses represent the number of participants that fit each statement. Note the number of analyzed participants matches the number of allocated participants, consistent with an intention-to-treat analysis
Fig. 2
Fig. 2
Change in walking speed. Box and whisker plots of change for A) comfortable and B) maximal walking speed from pre- to post-assessment (left column) and from pre- to 3-month assessment (right column). Small dots represent individual data, while large dots represent the minimum and maximum values. Gray dots represent mean values. Boxes range from the 1st to the 3rd quartile, and the middle horizontal lines represent the median values. The gray horizontal line at 0.16 m/s denotes the change in walking speed that meets MCID
Fig. 3
Fig. 3
HISTT weekly measures. Weekly values for A) maximal overground walking speed were tested at the start of each training week. Weekly values for B) peak treadmill walking speed, C) distance walked, D) peak heart rate, and E) peak Borg 0–10 Rating of Perceived Exertion (RPE) are the average across the three training sessions within the respective week. Group mean ± SE is shown
Fig. 4
Fig. 4
tDCS responsiveness. Box plots of change in A) comfortable and B) maximal walking speed from pre- to post-assessment (left column) and from pre- to 3-month assessment (right column). *p < 0.05 between up-regulators and down-regulators

References

    1. Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Recovery of walking function in stroke patients: the Copenhagen stroke study. Arch Phys Med Rehabil. 1995;76(1):27–32.
    1. Turnbull GI, Charteris J, Wall JC. A comparison of the range of walking speeds between normal and hemiplegic subjects. Scand J Rehabil Med. 1995;27(3):175–182.
    1. Salbach NM, O'Brien K, Brooks D, Irvin E, Martino R, Takhar P, et al. Speed and distance requirements for community ambulation: a systematic review. Arch Phys Med Rehabil. 2014;95(1):117–128.
    1. Mayo NE, Wood-Dauphinee S, Ahmed S, Gordon C, Higgins J, McEwen S, et al. Disablement following stroke. Disabil Rehabil. 1999;21(5–6):258–268.
    1. Robinson CA, Shumway-Cook A, Matsuda PN, Ciol MA. Understanding physical factors associated with participation in community ambulation following stroke. Disabil Rehabil. 2011;33(12):1033–1042.
    1. English C, Manns PJ, Tucak C, Bernhardt J. Physical activity and sedentary behaviors in people with stroke living in the community: a systematic review. Phys Ther. 2014;94(2):185–196.
    1. Mayo NE, Wood-Dauphinee S, Cote R, Durcan L, Carlton J. Activity, participation, and quality of life 6 months poststroke. Arch Phys Med Rehabil. 2002;83(8):1035–1042.
    1. Khanittanuphong P, Tipchatyotin S. Correlation of the gait speed with the quality of life and the quality of life classified according to speed-based community ambulation in Thai stroke survivors. NeuroRehabilitation. 2017;41(1):135–141.
    1. Polese JC, Ada L, Dean CM, Nascimento LR, Teixeira-Salmela LF. Treadmill training is effective for ambulatory adults with stroke: a systematic review. J Physiother. 2013;59(2):73–80.
    1. Gibala MJ, Little JP, Macdonald MJ, Hawley JA. Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol. 2012;590(5):1077–1084.
    1. Pohl M, Mehrholz J, Ritschel C, Ruckriem S. Speed-dependent treadmill training in ambulatory hemiparetic stroke patients: a randomized controlled trial. Stroke. 2002;33(2):553–558.
    1. Boyne P, Dunning K, Carl D, Gerson M, Khoury J, Rockwell B, et al. High-intensity interval training and moderate-intensity continuous training in ambulatory chronic stroke: feasibility study. Phys Ther. 2016;96(10):1533–1544.
    1. Lau KW, Mak MK. Speed-dependent treadmill training is effective to improve gait and balance performance in patients with sub-acute stroke. J Rehabil Med. 2011;43(8):709–713.
    1. Stoykov ME, Madhavan S. Motor priming in neurorehabilitation. J Neurol Phys Ther. 2015;39(1):33–42.
    1. Reis J, Robertson EM, Krakauer JW, Rothwell J, Marshall L, Gerloff C, et al. Consensus: can transcranial direct current stimulation and transcranial magnetic stimulation enhance motor learning and memory formation? Brain Stimul. 2008;1(4):363–369.
    1. Madhavan S, Shah B. Enhancing motor skill learning with transcranial direct current stimulation - a concise review with applications to stroke. Front Psychiatry. 2012;3:66.
    1. Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, et al. Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci. 2003;15(4):619–626.
    1. Stoykov ME, Corcos DM, Madhavan S. Movement-based priming: clinical applications and neural mechanisms. J Mot Behav. 2017;49(1):88–97.
    1. Stinear CM, Petoe MA, Anwar S, Barber PA, Byblow WD. Bilateral priming accelerates recovery of upper limb function after stroke: a randomized controlled trial. Stroke. 2014;45(1):205–210.
    1. Madhavan S, Stinear JW, Kanekar N. Effects of a single session of high intensity interval treadmill training on Corticomotor excitability following stroke: implications for therapy. Neural Plast. 2016;2016:1686414.
    1. Proschan MA, Lan KKG, Wittes JT. Statistical monitoring of clinical trials : a unified approach. New York, NY: Springer; 2006. xiii, 258 p. p.
    1. Madhavan S, Rogers LM, Stinear JW. A paradox: after stroke, the non-lesioned lower limb motor cortex may be maladaptive. Eur J Neurosci. 2010;32(6):1032–1039.
    1. Madhavan S, Weber KA, 2nd, Stinear JW. Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation. Exp Brain Res. 2011;209(1):9–17.
    1. Madhavan S, Lim H, Sivaramakrishnan A, Iyer P. Effects of high intensity speed-based treadmill training on ambulatory function in people with chronic stroke: a preliminary study with long-term follow-up. Sci Rep. 2019;9(1):1985.
    1. Madhavan S, Stinear JW. Focal and bi-directional modulation of lower limb motor cortex using anodal transcranial direct current stimulation. Brain Stimul. 2010;3(1):42.
    1. Sivaramakrishnan A, Tahara-Eckl L, Madhavan S. Spatial localization and distribution of the TMS-related 'hotspot' of the tibialis anterior muscle representation in the healthy and post-stroke motor cortex. Neurosci Lett. 2016;627:30–35.
    1. Madhavan S, Sriraman A, Freels S. Reliability and Variability of tDCS Induced Changes in the Lower Limb Motor Cortex. Brain Sci. 2016;6(3).
    1. Wiethoff S, Hamada M, Rothwell JC. Variability in response to transcranial direct current stimulation of the motor cortex. Brain Stimul. 2014;7(3):468–475.
    1. Gjellesvik TI, Brurok B, Hoff J, Torhaug T, Helgerud J. Effect of high aerobic intensity interval treadmill walking in people with chronic stroke: a pilot study with one year follow-up. Top Stroke Rehabil. 2012;19(4):353–360.
    1. Askim T, Dahl AE, Aamot IL, Hokstad A, Helbostad J, Indredavik B. High-intensity aerobic interval training for patients 3-9 months after stroke: a feasibility study. Physiother Res Int. 2014;19(3):129–139.
    1. Macko RF, Ivey FM, Forrester LW, Hanley D, Sorkin JD, Katzel LI, et al. Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: a randomized, controlled trial. Stroke. 2005;36(10):2206–2211.
    1. Luft AR, Macko RF, Forrester LW, Villagra F, Ivey F, Sorkin JD, et al. Treadmill exercise activates subcortical neural networks and improves walking after stroke: a randomized controlled trial. Stroke. 2008;39(12):3341–3350.
    1. Boddington LJ, Reynolds JN. Targeting interhemispheric inhibition with neuromodulation to enhance stroke rehabilitation. Brain Stimul. 2017;10(2):214–222.
    1. Duque J, Hummel F, Celnik P, Murase N, Mazzocchio R, Cohen LG. Transcallosal inhibition in chronic subcortical stroke. Neuroimage. 2005;28(4):940–946.
    1. Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol. 2004;55(3):400–409.
    1. Jayaram G, Stinear JW. The effects of transcranial stimulation on paretic lower limb motor excitability during walking. J Clin Neurophysiol. 2009;26(4):272–279.
    1. Jeffery DT, Norton JA, Roy FD, Gorassini MA. Effects of transcranial direct current stimulation on the excitability of the leg motor cortex. Exp Brain Res. 2007;182(2):281–287.
    1. Khedr EM, Shawky OA, El-Hammady DH, Rothwell JC, Darwish ES, Mostafa OM, et al. Effect of anodal versus cathodal transcranial direct current stimulation on stroke rehabilitation: a pilot randomized controlled trial. Neurorehabil Neural Repair. 2013;27(7):592–601.
    1. Tanaka S, Takeda K, Otaka Y, Kita K, Osu R, Honda M, et al. Single session of transcranial direct current stimulation transiently increases knee extensor force in patients with hemiparetic stroke. Neurorehabil Neural Repair. 2011;25(6):565–569.
    1. Tahtis V, Kaski D, Seemungal BM. The effect of single session bi-cephalic transcranial direct current stimulation on gait performance in sub-acute stroke: a pilot study. Restor Neurol Neurosci. 2014;32(4):527–532.
    1. Sohn MK, Jee SJ, Kim YW. Effect of transcranial direct current stimulation on postural stability and lower extremity strength in hemiplegic stroke patients. Ann Rehabil Med. 2013;37(6):759–765.
    1. Geroin C, Picelli A, Munari D, Waldner A, Tomelleri C, Smania N. Combined transcranial direct current stimulation and robot-assisted gait training in patients with chronic stroke: a preliminary comparison. Clin Rehabil. 2011;25(6):537–548.
    1. Danzl MM, Chelette KC, Lee K, Lykins D, Sawaki L. Brain stimulation paired with novel locomotor training with robotic gait orthosis in chronic stroke: a feasibility study. NeuroRehabilitation. 2013;33(1):67–76.
    1. Leon D, Cortes M, Elder J, Kumru H, Laxe S, Edwards DJ, et al. tDCS does not enhance the effects of robot-assisted gait training in patients with subacute stroke. Restor Neurol Neurosci. 2017;35(4):377–384.
    1. Seo HG, Lee WH, Lee SH, Yi Y, Kim KD, Oh BM. Robotic-assisted gait training combined with transcranial direct current stimulation in chronic stroke patients: a pilot double-blind, randomized controlled trial. Restor Neurol Neurosci. 2017;35(5):527–536.
    1. Manji A, Amimoto K, Matsuda T, Wada Y, Inaba A, Ko S. Effects of transcranial direct current stimulation over the supplementary motor area body weight-supported treadmill gait training in hemiparetic patients after stroke. Neurosci Lett. 2018;662:302–305.
    1. Park SD, Kim JY, Song HS. Effect of application of transcranial direct current stimulation during task-related training on gait ability of patients with stroke. J Phys Ther Sci. 2015;27(3):623–625.
    1. Picelli A, Chemello E, Castellazzi P, Roncari L, Waldner A, Saltuari L, et al. Combined effects of transcranial direct current stimulation (tDCS) and transcutaneous spinal direct current stimulation (tsDCS) on robot-assisted gait training in patients with chronic stroke: a pilot, double blind, randomized controlled trial. Restor Neurol Neurosci. 2015;33(3):357–368.
    1. Chang MC, Kim DY, Park DH. Enhancement of cortical excitability and lower limb motor function in patients with stroke by transcranial direct current stimulation. Brain Stimul. 2015;8(3):561–566.
    1. Fusco A, Assenza F, Iosa M, Izzo S, Altavilla R, Paolucci S, et al. The ineffective role of cathodal tDCS in enhancing the functional motor outcomes in early phase of stroke rehabilitation: an experimental trial. Biomed Res Int. 2014;2014:547290.
    1. Ardestani MM, Kinnaird CR, Henderson CE, Hornby TG. Compensation or recovery? Altered kinetics and neuromuscular synergies following high-intensity stepping training Poststroke. Neurorehabil Neural Repair. 2019;33(1):47–58.
    1. Mahtani GB, Kinnaird CR, Connolly M, Holleran CL, Hennessy PW, Woodward J, et al. Altered sagittal- and frontal-plane kinematics following high-intensity stepping training versus conventional interventions in subacute stroke. Phys Ther. 2017;97(3):320–329.
    1. Saeys W, Vereeck L, Lafosse C, Truijen S, Wuyts FL, Van De Heyning P. Transcranial direct current stimulation in the recovery of postural control after stroke: a pilot study. Disabil Rehabil. 2015;37(20):1857–1863.
    1. Ojardias E, Aze OD, Luneau D, Mednieks J, Condemine A. Rimaud D, et al. Neuromodulation: The Effects of Anodal Transcranial Direct Current Stimulation on the Walking Performance of Chronic Hemiplegic Patients; 2019.
    1. Cattagni T, Geiger M, Supiot A, de Mazancourt P, Pradon D, Zory R, et al. A single session of anodal transcranial direct current stimulation applied over the affected primary motor cortex does not alter gait parameters in chronic stroke survivors. Neurophysiol Clin. 2019;49(4):283–293.
    1. Kindred JH, Kautz SA, Wonsetler EC, Bowden MG. Single sessions of high-definition transcranial direct current stimulation do not Alter lower extremity biomechanical or Corticomotor response variables post-stroke. Front Neurosci. 2019;13:286.
    1. Dietz V. Spinal cord pattern generators for locomotion. Clin Neurophysiol. 2003;114(8):1379–1389.
    1. Picelli A, Chemello E, Castellazzi P, Filippetti M, Brugnera A, Gandolfi M, et al. Combined effects of cerebellar transcranial direct current stimulation and transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke: a pilot, single blind, randomized controlled trial. Restor Neurol Neurosci. 2018;36(2):161–171.
    1. Horvath JC, Carter O, Forte JD. Transcranial direct current stimulation: five important issues we aren't discussing (but probably should be) Front Syst Neurosci. 2014;8:2.
    1. Dissanayaka T, Zoghi M, Farrell M, Egan GF, Jaberzadeh S. Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta-analysis. Eur J Neurosci. 2017;46(4):1968–1990.
    1. Plow EB, Sankarasubramanian V, Cunningham DA, Potter-Baker K, Varnerin N, Cohen LG, et al. Models to tailor brain stimulation therapies in stroke. Neural Plast. 2016;2016:4071620.
    1. Russo C, Souza Carneiro MI, Bolognini N, Fregni F. Safety review of transcranial direct current stimulation in stroke. Neuromodulation. 2017;20(3):215–222.
    1. Crozier J, Roig M, Eng JJ, MacKay-Lyons M, Fung J, Ploughman M, et al. High-intensity interval training after stroke: an opportunity to promote functional recovery, cardiovascular health, and neuroplasticity. Neurorehabil Neural Repair. 2018;32(6–7):543–556.
    1. Carl DL, Boyne P, Rockwell B, Gerson M, Khoury J, Kissela B, et al. Preliminary safety analysis of high-intensity interval training (HIIT) in persons with chronic stroke. Appl Physiol Nutr Metab. 2017;42(3):311–318.
    1. Van de Winckel A, Carey JR, Bisson TA, Hauschildt EC, Streib CD, Durfee WK. Home-based transcranial direct current stimulation plus tracking training therapy in people with stroke: an open-label feasibility study. J Neuroeng Rehabil. 2018;15(1):83.
    1. Steen Krawcyk R, Vinther A, Petersen NC, Faber J, Iversen HK, Christensen T, et al. Effect of home-based high-intensity interval training in patients with lacunar stroke: a randomized controlled trial. Front Neurol. 2019;10:664.

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