The effect of Transcranial direct current stimulation (tDCS) on the lower limb function with and without Step exercise in chronic stroke patients: a randomized control clinical trial

authors:

avatar Roghayeh Mohammadi ORCID , avatar Sajjad Ramezani , avatar Mohammadreza Mohammadi , avatar Elham Fatemi , *


how to cite: Mohammadi R, Ramezani S, Mohammadi M, Fatemi E. The effect of Transcranial direct current stimulation (tDCS) on the lower limb function with and without Step exercise in chronic stroke patients: a randomized control clinical trial. koomesh. 2021;23(3):e149950. 

Abstract

Introduction: The aim of this study was to investigate the effect of one-session transcranial direct current stimulation  (tDCS) of cerebral cortex with and without step practice on foot function in patients with chronic stroke. Materials and Methods: It was an interventional and clinical trial study. Forty patients with chronic stroke were randomly assigned into four groups, Sham tDCS, tDCS, tDCS + Step exercise, and Step exercise. Timed up and go test was carried out with asymmetrical position of feet, affected leg behind of the unaffected leg before and after of intervention. In this way, anodal tDCS (2 mA) was applied over the primary motor cortex for 20 minutes. Results: The interactive effect between time and groups has been significant (P=0.002, effect size=0.36). The follow-up test showed that the Timed up and go test time did not show a significant difference between the other groups after the intervention (P

References

  • 1.

    [1] Lendraitien E, Tamoauskait A, Petrueviien D, Savickas R. Balance evaluation techniques and physical therapy in post-stroke patients: A literature review. Neurol Neurochir Pol 2017; 51: 92-100.

  • 2.

    https://doi.org/10.1016/j.pjnns.2016.11.003.

  • 3.

    PMid:27884459.

  • 4.

    [2] Roy G, Nadeau S, Gravel D, Malouin F, McFadyen BJ, Piotte F. The effect of foot position and chair height on the asymmetry of vertical forces during sit-to-stand and stand-to-sit tasks in individuals with hemiparesis. Clin Biomech (Bristol, Avon) 2006; 21: 585-593.

  • 5.

    https://doi.org/10.1016/j.clinbiomech.2006.01.007.

  • 6.

    PMid:16540217.

  • 7.

    [3] Ng SS, Hui-Chan CW. The timed up & go test: its reliability and association with lower-limb impairments and locomotor capacities in people with chronic stroke. Arch Phys Med Rehabil 2005; 86: 1641-1647.

  • 8.

    https://doi.org/10.1016/j.apmr.2005.01.011.

  • 9.

    PMid:16084820.

  • 10.

    [4] Joshua AM, Karnad SD, Nayak A, Suresh BV, Mithra P, Unnikrishnan B. Effect of foot placements during sit to stand transition on timed up and go test in stroke subjects: A cross sectional study. NeuroRehabilitation 2017; 40: 355-362.

  • 11.

    https://doi.org/10.3233/NRE-161423.

  • 12.

    PMid:28222557.

  • 13.

    [5] Han J, Kim Y, Kim K. Effects of foot position of the nonparetic side during sit-to-stand training on postural balance in patients with stroke. J Phys Ther Sci 2015; 27: 2625-2627.

  • 14.

    https://doi.org/10.1589/jpts.27.2625.

  • 15.

    PMid:26356809 PMCid:PMC4563329.

  • 16.

    [6] 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.

  • 17.

    https://doi.org/10.1016/j.neulet.2017.10.049.

  • 18.

    PMid:29107706.

  • 19.

    [7] Kang N, Lee RD, Lee JH, Hwang MH. Functional balance and postural control improvements in patients with stroke after noninvasive brain stimulation: a Meta-analysis. Arch Phys Med Rehabil 2020; 101: 141-153.

  • 20.

    https://doi.org/10.1016/j.apmr.2019.09.003.

  • 21.

    PMid:31568760.

  • 22.

    [8] Cha H-K, Ji SG, Kim MK, Chang JS. Effect of transcranial direct current stimulation of function in patients with stroke. J Phys Ther Sci 2014; 26: 363-365.

  • 23.

    https://doi.org/10.1589/jpts.26.363.

  • 24.

    PMid:24707084 PMCid:PMC3976003.

  • 25.

    [9] Ojardias E, Aze OD, Luneau D, Mednieks J, Condemine A, Rimaud D, et al. The effects of anodal transcranial direct current stimulation on the walking performance of chronic hemiplegic patients. Neuromodulation 2020; 23: 373-379.

  • 26.

    https://doi.org/10.1111/ner.12962.

  • 27.

    PMid:31124218.

  • 28.

    [10] Li Y, Fan J, Yang J, He C, Li S. Effects of transcranial direct current stimulation on walking ability after stroke: A systematic review and meta-analysis. Restor Neurol Neurosci 2018; 36: 59-71.

  • 29.

    https://doi.org/10.3233/RNN-170770.

  • 30.

    PMid:29439362.

  • 31.

    [11] Grecco LA, Duarte NA, Zanon N, Galli M, Fregni F, Oliveira CS. Effect of a single session of transcranial direct-current stimulation on balance and spatiotemporal gait variables in children with cerebral palsy: a randomized sham-controlled study. Braz J Phys Ther 2014; 18: 419-427.

  • 32.

    https://doi.org/10.1590/bjpt-rbf.2014.0053.

  • 33.

    PMid:25372004 PMCid:PMC4228627.

  • 34.

    [12] Klomjai W, Aneksan B, Pheungphrarattanatrai A, Chantanachai T, Choowong N, Bunleukhet S, et al. Effect of single-session dual-tDCS before physical therapy on lower-limb performance in sub-acute stroke patients: A randomized sham-controlled crossover study. Ann Phys Rehabil Med 2018; 61: 286-291.

  • 35.

    https://doi.org/10.1016/j.rehab.2018.04.005.

  • 36.

    PMid:29763676.

  • 37.

    [13] Dumont AJ, Araujo MC, Lazzari RD, Santos CA, Carvalho DB, Franco de Moura RC, et al. Effects of a single session of transcranial direct current stimulation on static balance in a patient with hemiparesis: a case study. J Phys Ther Sci 2015; 27: 955-958.

  • 38.

    https://doi.org/10.1589/jpts.27.955.

  • 39.

    PMid:25931768 PMCid:PMC4395752.

  • 40.

    [14] Liu M, Chen J, Fan W, Mu J, Zhang J, Wang L, et al. Effects of modified sit-to-stand training on balance control in hemiplegic stroke patients: a randomized controlled trial. Clin Rehabil 2016; 30: 627-636.

  • 41.

    https://doi.org/10.1177/0269215515600505.

  • 42.

    PMid:26316551.

  • 43.

    [15] Pascual-Leone A, Tormos JM, Keenan J, Tarazona F, Canete C, Catala MD. Study and modulation of human cortical excitability with transcranial magnetic stimulation. J Clin Neurophysiol 1998; 15: 333-343.

  • 44.

    https://doi.org/10.1097/00004691-199807000-00005.

  • 45.

    PMid:9736467.

  • 46.

    [16] Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol 2006; 117: 1623-1629.

  • 47.

    https://doi.org/10.1016/j.clinph.2006.04.009.

  • 48.

    PMid:16762592.

  • 49.

    [17] Villamar MF, Volz MS, Bikson M, Datta A, Dasilva AF, Fregni F. Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS). J Vis Exp 2013; 77: e50309.

  • 50.

    https://doi.org/10.3791/50309.

  • 51.

    PMid:23893039 PMCid:PMC3735368.

  • 52.

    [18] Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol 2006; 117: 845-850.

  • 53.

    https://doi.org/10.1016/j.clinph.2005.12.003.

  • 54.

    PMid:16427357.

  • 55.

    [19] Lang N, Nitsche MA, Paulus W, Rothwell JC, Lemon RN. Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res 2004; 156: 439-443.

  • 56.

    https://doi.org/10.1007/s00221-003-1800-2.

  • 57.

    PMid:14745467.

  • 58.

    [20] Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain 2005; 128: 490-499.

  • 59.

    https://doi.org/10.1093/brain/awh369.

  • 60.

    PMid:15634731.

  • 61.

    [21] Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, et al. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport 2005; 16: 1551-1555.

  • 62.

    https://doi.org/10.1097/01.wnr.0000177010.44602.5e.

  • 63.

    PMid:16148743.

  • 64.

    [22] 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: 565-569.

  • 65.

    https://doi.org/10.1177/1545968311402091.

  • 66.

    PMid:21436391.

  • 67.

    [23] 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: 759-765.

  • 68.

    https://doi.org/10.5535/arm.2013.37.6.759.

  • 69.

    PMid:24466510 PMCid:PMC3895515.

  • 70.

    [24] Zhou J, Hao Y, Wang Y, Jor'dan A, Pascual-Leone A, Zhang J, et al. Transcranial direct current stimulation reduces the cost of performing a cognitive task on gait and postural control. Eur J Neurosci 2014; 39: 1343-1348.

  • 71.

    https://doi.org/10.1111/ejn.12492.

  • 72.

    PMid:24443958 PMCid:PMC4221849.

  • 73.

    [25] Grecco LA, Duarte NA, Zanon N, Galli M, Fregni F, Oliveira CS. Effect of a single session of transcranial direct-current stimulation on balance and spatiotemporal gait variables in children with cerebral palsy: A randomized sham-controlled study. Braz J Phys Ther 2014; 18: 419-427.

  • 74.

    https://doi.org/10.1590/bjpt-rbf.2014.0053.

  • 75.

    PMid:25372004 PMCid:PMC4228627.

  • 76.

    [26] Wagner T, Fregni F, Fecteau S, Grodzinsky A, Zahn M, Pascual-Leone A. Transcranial direct current stimulation: a computer-based human model study. Neuroimage 2007; 35: 1113-1124.

  • 77.

    https://doi.org/10.1016/j.neuroimage.2007.01.027.

  • 78.

    PMid:17337213.

  • 79.

    [27] Janssen W, Bussmann J, Selles R, Koudstaal P, Ribbers G, Stam H. Recovery of the sit-to-stand movement after stroke: a longitudinal cohort study. Neurorehabil Neural Repair 2010; 24: 763-769.

  • 80.

    https://doi.org/10.1177/1545968310363584.

  • 81.

    PMid:20702392.

  • 82.

    [28] Duclos C, Nadeau S, Lecours J. Lateral trunk displacement and stability during sit-to-stand transfer in relation to foot placement in patients with hemiparesis. Neurorehabil Neural Repair 2008; 22: 715-722.

  • 83.

    https://doi.org/10.1177/1545968308316000.

  • 84.

    PMid:18812434.

  • 85.

    [29] Kim K, Kim YM, Kang DY. Repetitive sit-to-stand training with the step-foot position on the non-paretic side, and its effects on the balance and foot pressure of chronic stroke subjects. J Phys Ther Sci 2015; 27: 2621-2624.

  • 86.

    https://doi.org/10.1589/jpts.27.2621.

  • 87.

    PMid:26357448 PMCid:PMC4563328.

  • 88.

    [30] Rocha Ade S, Knabben RJ, Michaelsen SM. Non-paretic lower limb constraint with a step decreases the asymmetry of vertical forces during sit-to-stand at two seat heights in subjects with hemiparesis. Gait Posture 2010; 32: 457-463.

  • 89.

    https://doi.org/10.1016/j.gaitpost.2010.07.001.

  • 90.

    PMid:20674364.

  • 91.

    [31] Gray CK, Culham E. Sit-to-Stand in People with Stroke: Effect of Lower Limb Constraint-Induced Movement Strategies. Stroke Res Treat 2014; 2014: 683681.

  • 92.

    https://doi.org/10.1155/2014/683681.

  • 93.

    PMid:24757576 PMCid:PMC3976795.

  • 94.

    [1] Lendraitien E, Tamoauskait A, Petrueviien D, Savickas R. Balance evaluation techniques and physical therapy in post-stroke patients: A literature review. Neurol Neurochir Pol 2017; 51: 92-100.

  • 95.

    https://doi.org/10.1016/j.pjnns.2016.11.003.

  • 96.

    PMid:27884459.

  • 97.

    [2] Roy G, Nadeau S, Gravel D, Malouin F, McFadyen BJ, Piotte F. The effect of foot position and chair height on the asymmetry of vertical forces during sit-to-stand and stand-to-sit tasks in individuals with hemiparesis. Clin Biomech (Bristol, Avon) 2006; 21: 585-593.

  • 98.

    https://doi.org/10.1016/j.clinbiomech.2006.01.007.

  • 99.

    PMid:16540217.

  • 100.

    [3] Ng SS, Hui-Chan CW. The timed up & go test: its reliability and association with lower-limb impairments and locomotor capacities in people with chronic stroke. Arch Phys Med Rehabil 2005; 86: 1641-1647.

  • 101.

    https://doi.org/10.1016/j.apmr.2005.01.011.

  • 102.

    PMid:16084820.

  • 103.

    [4] Joshua AM, Karnad SD, Nayak A, Suresh BV, Mithra P, Unnikrishnan B. Effect of foot placements during sit to stand transition on timed up and go test in stroke subjects: A cross sectional study. NeuroRehabilitation 2017; 40: 355-362.

  • 104.

    https://doi.org/10.3233/NRE-161423.

  • 105.

    PMid:28222557.

  • 106.

    [5] Han J, Kim Y, Kim K. Effects of foot position of the nonparetic side during sit-to-stand training on postural balance in patients with stroke. J Phys Ther Sci 2015; 27: 2625-2627.

  • 107.

    https://doi.org/10.1589/jpts.27.2625.

  • 108.

    PMid:26356809 PMCid:PMC4563329.

  • 109.

    [6] 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.

  • 110.

    https://doi.org/10.1016/j.neulet.2017.10.049.

  • 111.

    PMid:29107706.

  • 112.

    [7] Kang N, Lee RD, Lee JH, Hwang MH. Functional balance and postural control improvements in patients with stroke after noninvasive brain stimulation: a Meta-analysis. Arch Phys Med Rehabil 2020; 101: 141-153.

  • 113.

    https://doi.org/10.1016/j.apmr.2019.09.003.

  • 114.

    PMid:31568760.

  • 115.

    [8] Cha H-K, Ji SG, Kim MK, Chang JS. Effect of transcranial direct current stimulation of function in patients with stroke. J Phys Ther Sci 2014; 26: 363-365.

  • 116.

    https://doi.org/10.1589/jpts.26.363.

  • 117.

    PMid:24707084 PMCid:PMC3976003.

  • 118.

    [9] Ojardias E, Aze OD, Luneau D, Mednieks J, Condemine A, Rimaud D, et al. The effects of anodal transcranial direct current stimulation on the walking performance of chronic hemiplegic patients. Neuromodulation 2020; 23: 373-379.

  • 119.

    https://doi.org/10.1111/ner.12962.

  • 120.

    PMid:31124218.

  • 121.

    [10] Li Y, Fan J, Yang J, He C, Li S. Effects of transcranial direct current stimulation on walking ability after stroke: A systematic review and meta-analysis. Restor Neurol Neurosci 2018; 36: 59-71.

  • 122.

    https://doi.org/10.3233/RNN-170770.

  • 123.

    PMid:29439362.

  • 124.

    [11] Grecco LA, Duarte NA, Zanon N, Galli M, Fregni F, Oliveira CS. Effect of a single session of transcranial direct-current stimulation on balance and spatiotemporal gait variables in children with cerebral palsy: a randomized sham-controlled study. Braz J Phys Ther 2014; 18: 419-427.

  • 125.

    https://doi.org/10.1590/bjpt-rbf.2014.0053.

  • 126.

    PMid:25372004 PMCid:PMC4228627.

  • 127.

    [12] Klomjai W, Aneksan B, Pheungphrarattanatrai A, Chantanachai T, Choowong N, Bunleukhet S, et al. Effect of single-session dual-tDCS before physical therapy on lower-limb performance in sub-acute stroke patients: A randomized sham-controlled crossover study. Ann Phys Rehabil Med 2018; 61: 286-291.

  • 128.

    https://doi.org/10.1016/j.rehab.2018.04.005.

  • 129.

    PMid:29763676.

  • 130.

    [13] Dumont AJ, Araujo MC, Lazzari RD, Santos CA, Carvalho DB, Franco de Moura RC, et al. Effects of a single session of transcranial direct current stimulation on static balance in a patient with hemiparesis: a case study. J Phys Ther Sci 2015; 27: 955-958.

  • 131.

    https://doi.org/10.1589/jpts.27.955.

  • 132.

    PMid:25931768 PMCid:PMC4395752.

  • 133.

    [14] Liu M, Chen J, Fan W, Mu J, Zhang J, Wang L, et al. Effects of modified sit-to-stand training on balance control in hemiplegic stroke patients: a randomized controlled trial. Clin Rehabil 2016; 30: 627-636.

  • 134.

    https://doi.org/10.1177/0269215515600505.

  • 135.

    PMid:26316551.

  • 136.

    [15] Pascual-Leone A, Tormos JM, Keenan J, Tarazona F, Canete C, Catala MD. Study and modulation of human cortical excitability with transcranial magnetic stimulation. J Clin Neurophysiol 1998; 15: 333-343.

  • 137.

    https://doi.org/10.1097/00004691-199807000-00005.

  • 138.

    PMid:9736467.

  • 139.

    [16] Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol 2006; 117: 1623-1629.

  • 140.

    https://doi.org/10.1016/j.clinph.2006.04.009.

  • 141.

    PMid:16762592.

  • 142.

    [17] Villamar MF, Volz MS, Bikson M, Datta A, Dasilva AF, Fregni F. Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS). J Vis Exp 2013; 77: e50309.

  • 143.

    https://doi.org/10.3791/50309.

  • 144.

    PMid:23893039 PMCid:PMC3735368.

  • 145.

    [18] Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol 2006; 117: 845-850.

  • 146.

    https://doi.org/10.1016/j.clinph.2005.12.003.

  • 147.

    PMid:16427357.

  • 148.

    [19] Lang N, Nitsche MA, Paulus W, Rothwell JC, Lemon RN. Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res 2004; 156: 439-443.

  • 149.

    https://doi.org/10.1007/s00221-003-1800-2.

  • 150.

    PMid:14745467.

  • 151.

    [20] Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain 2005; 128: 490-499.

  • 152.

    https://doi.org/10.1093/brain/awh369.

  • 153.

    PMid:15634731.

  • 154.

    [21] Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, et al. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport 2005; 16: 1551-1555.

  • 155.

    https://doi.org/10.1097/01.wnr.0000177010.44602.5e.

  • 156.

    PMid:16148743.

  • 157.

    [22] 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: 565-569.

  • 158.

    https://doi.org/10.1177/1545968311402091.

  • 159.

    PMid:21436391.

  • 160.

    [23] 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: 759-765.

  • 161.

    https://doi.org/10.5535/arm.2013.37.6.759.

  • 162.

    PMid:24466510 PMCid:PMC3895515.

  • 163.

    [24] Zhou J, Hao Y, Wang Y, Jor'dan A, Pascual-Leone A, Zhang J, et al. Transcranial direct current stimulation reduces the cost of performing a cognitive task on gait and postural control. Eur J Neurosci 2014; 39: 1343-1348.

  • 164.

    https://doi.org/10.1111/ejn.12492.

  • 165.

    PMid:24443958 PMCid:PMC4221849.

  • 166.

    [25] Grecco LA, Duarte NA, Zanon N, Galli M, Fregni F, Oliveira CS. Effect of a single session of transcranial direct-current stimulation on balance and spatiotemporal gait variables in children with cerebral palsy: A randomized sham-controlled study. Braz J Phys Ther 2014; 18: 419-427.

  • 167.

    https://doi.org/10.1590/bjpt-rbf.2014.0053.

  • 168.

    PMid:25372004 PMCid:PMC4228627.

  • 169.

    [26] Wagner T, Fregni F, Fecteau S, Grodzinsky A, Zahn M, Pascual-Leone A. Transcranial direct current stimulation: a computer-based human model study. Neuroimage 2007; 35: 1113-1124.

  • 170.

    https://doi.org/10.1016/j.neuroimage.2007.01.027.

  • 171.

    PMid:17337213.

  • 172.

    [27] Janssen W, Bussmann J, Selles R, Koudstaal P, Ribbers G, Stam H. Recovery of the sit-to-stand movement after stroke: a longitudinal cohort study. Neurorehabil Neural Repair 2010; 24: 763-769.

  • 173.

    https://doi.org/10.1177/1545968310363584.

  • 174.

    PMid:20702392.

  • 175.

    [28] Duclos C, Nadeau S, Lecours J. Lateral trunk displacement and stability during sit-to-stand transfer in relation to foot placement in patients with hemiparesis. Neurorehabil Neural Repair 2008; 22: 715-722.

  • 176.

    https://doi.org/10.1177/1545968308316000.

  • 177.

    PMid:18812434.

  • 178.

    [29] Kim K, Kim YM, Kang DY. Repetitive sit-to-stand training with the step-foot position on the non-paretic side, and its effects on the balance and foot pressure of chronic stroke subjects. J Phys Ther Sci 2015; 27: 2621-2624.

  • 179.

    https://doi.org/10.1589/jpts.27.2621.

  • 180.

    PMid:26357448 PMCid:PMC4563328.

  • 181.

    [30] Rocha Ade S, Knabben RJ, Michaelsen SM. Non-paretic lower limb constraint with a step decreases the asymmetry of vertical forces during sit-to-stand at two seat heights in subjects with hemiparesis. Gait Posture 2010; 32: 457-463.

  • 182.

    https://doi.org/10.1016/j.gaitpost.2010.07.001.

  • 183.

    PMid:20674364.

  • 184.

    [31] Gray CK, Culham E. Sit-to-Stand in People with Stroke: Effect of Lower Limb Constraint-Induced Movement Strategies. Stroke Res Treat 2014; 2014: 683681.

  • 185.

    https://doi.org/10.1155/2014/683681.

  • 186.

    PMid:24757576 PMCid:PMC3976795.