Feasibility of Simultaneous Transcranial Direct Current Stimulation During Gait Training in Chronic Stroke Patients: A Randomized Double-blind Pilot Clinical Trial

Feasibility of Simultaneous Transcranial Direct Current Stimulation During Gait Training in Chronic Stroke Patients: A Randomized Double-blind Pilot Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Feasibility of Simultaneous Transcranial Direct Current Stimulation During Gait Training in Chronic Stroke Patients: A Randomized Double-blind Pilot Clinical Trial Hyeong-Min Kim, Ji-Min Na, Hyun-Seok Jo, Min-Keun Song, Hyeng-Kyu Park, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4173477/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Transcranial direct current stimulation (tDCS) is a therapeutic tool for improving post-stroke gait disturbances, with ongoing research focusing on specific protocols for its application. We evaluated the feasibility of a rehabilitation protocol that combines tDCS with conventional gait training. Methods This was a randomized, double-blind, single-center pilot clinical trial. Patients with unilateral hemiplegia due to ischemic stroke were randomly assigned to either the tDCS with gait training group or the sham stimulation group. The anodal tDCS electrode was placed on the tibialis anterior area of the precentral gyrus while gait training proceeded. Interventions were administered 3 times weekly for 4 weeks. Outcome assessments, using the 10-meter walk test, Timed Up and Go test, Berg Balance Scale, Functional Ambulatory Scale, Modified Barthel Index, and EQ-5D-3L, were conducted before and after the intervention and again at the 8-week mark following its completion. Repeated-measures ANOVA was used for comparisons between and within groups. Results Twenty-six patients were assessed for eligibility, and 20 were enrolled and randomized. No significant differences were observed between the tDCS with gait training group and the sham stimulation group in gait speed after the intervention. However, the tDCS with gait training group showed significant improvement in balance performance in both within-group and between-group comparisons. In the subgroup analysis of patients with elicited motor-evoked potentials, comfortable pace gait speed improved in the tDCS with gait training group. No serious adverse events occurred throughout the study. Conclusions Simultaneous tDCS during gait training is a feasible rehabilitation protocol for chronic stroke patients with gait disturbances. Trial registration: URL: https://cris.nih.go.kr ; Registration number: KCT0007601; Date of registration: 11 July 2022 gait disturbance stroke rehabilitation transcranial direct current stimulation Figures Figure 1 Figure 2 Introduction Impairment of independent gait is one of the most disabling consequences after a stroke [ 1 ]. Gait abnormality in stroke patients arises from a complex interplay of factors, including lower limb motor weakness and decreased balance. Some individuals may not be entirely incapable of walking, but they may still require gait aids or assistance from caregivers. Gait disturbances pose a greater risk of further injury due to falls. It is well known that fall-associated fractures result in significant socioeconomic costs [ 2 ]. Additionally, gait disturbances lead to limitations in social activity, thereby reducing the quality of life of stroke patients. Therefore, improving gait performance in stroke patients has long been a desire shared by patients and physicians. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that aims to modulate the human brain by delivering low-intensity electrical current through the scalp. The mechanism of tDCS is explained by 2 principles: (1) the enhancement of cortical activity through a polarity shift in the resting membrane potential and (2) the upregulation of neural plasticity through long-term potentiation [ 3 ]. Applying anodal tDCS to patients with subacute stroke has been associated with beneficial effects on motor function [ 4 ]. However, inconsistent results have emerged across studies, with some failing to observe significant improvements in patients who underwent tDCS compared to sham stimulation [ 5 ]. Additionally, there has been substantial variability in factors, such as stimulation area, intensity, duration, and the number of sessions among different tDCS protocols, highlighting the need for further research to establish an optimal tDCS protocol for maximizing the effect of conventional gait training methods. Studies focusing on stimulation timing suggest that combining tDCS with gait training simultaneously shows more promising results in improving gait performance compared to protocols that administer gait training and tDCS separately [ 6 ]. This study aimed to evaluate the feasibility of a rehabilitation protocol that combines simultaneous tDCS with conventional gait training and to investigate its impact on gait performance in chronic stroke patients. Methods Study Design This was a randomized, double-blind, single-center pilot clinical trial. We prospectively enrolled chronic stroke patients who visited the Department of Physical and Rehabilitation Medicine at Chonnam National University Hospital (Gwangju City, Korea) in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. Written informed consent was obtained from all participants before study enrollment. The study protocol was approved by the Medical Research Ethics Committee of Chonnam National University Hospital, adhering to the principles defined in the Declaration of Helsinki (1964). Participants The inclusion criteria were as follows: (1) patients aged 20 to 90 years; (2) ischemic stroke more than 3 months from onset; (3) unilateral hemiplegia at the time of evaluation; and (4) a functional ambulatory category grade between 2 and 4. The exclusion criteria were (1) diagnosis or concomitant hemorrhagic stroke; (2) gait disturbance resulting from other neurodegenerative, neuromuscular, or musculoskeletal conditions; (3) contraindications to electrostimulation, such as metallic implants in the head, craniectomy status, ongoing treatment for epilepsy, pregnancy, and malignancy; and (4) serious medical conditions that lead to unstable vital signs. All eligible patients were randomly assigned to 2 groups: (1) the experimental group, receiving gait training with tDCS (GtDCS), or (2) the control group, receiving gait training with sham stimulation (Gsham). Simple randomization method was adopted, and random allocation software 2.0 program used to generate the random allocation sequence. This study blinded the participants, outcome evaluator. The outcome evaluator is not allowed to contact the participants and clinical trial coordinator who manages the treatment except during the evaluation period Procedures 1) Electrode Placement Configuration We identified the appropriate scalp area for attaching electrodes to effectively deliver electrical stimulation to the target cerebral cortical area. To locate the position of the primary motor cortex responsible for leg movement, we recorded motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) at the hemiparetic tibialis anterior muscle. Magstim Rapid2® (Magstim Company Ltd., Whitland, UK) with a 9-cm circular coil was used to perform TMS. According to the international 10–20 system, Cz was set as the reference point on the patient's scalp. The magnetic stimulation was conducted four times at each site with 1-cm intervals toward the affected cortex from Cz. The stimulation intensity was applied at 100% of the maximum output of the TMS device. During stimulation, the location where the peak-to-peak amplitude of the MEP was greatest was assumed to be the tibialis anterior area of the precentral gyrus. The horizontal and vertical distances from Cz to this point were recorded. MEP recordings through TMS were conducted by a blinded examiner who was unaware of the patient's clinical information. 2) tDCS Application The HDCstim® (Newronika, Milan, Italy) device and two saline-soaked sponge surface electrodes, each measuring 25 cm 2 , were used to deliver the electrical current. The center of the anodal electrode was placed above the tibialis anterior area of the precentral gyrus, as confirmed by the MEP evaluation. If MEPs were not induced, the anodal electrode was placed above C3 or C4 according to the international 10–20 system. The cathodal electrode was positioned on the contralateral supraorbital area. In the GtDCS group, patients received tDCS at an intensity of 2.0 mA for 20 minutes during gait training. In the Gsham group, no electrical current was delivered, except for sham stimulation lasting 15 seconds at the beginning and end of the gait training session. During sham stimulation, the stimulator remained operating, rendering it impossible for participants to discern whether they were receiving true brain stimulation. 3) Gait Training All patients participated in the gait training program, which consisted of 10 minutes of simple gait training and 10 minutes of complex gait training. The simple gait training involved walking on flat ground, while the complex gait training included activities such as stair climbing, sideways walking, and walking backward. Individuals for whom complex gait training was deemed infeasible due to impaired gait performance engaged in 20 minutes of simple gait training. Assistive walking devices were used as needed during the sessions. The entire training process was conducted under the supervision and assistance of skilled physical therapists, who remained blinded to the patients’ group allocations. The intervention, including gait training and tDCS, was carried out over 12 sessions: 3 times a week for 4 weeks. Outcomes The primary outcome measure was the 10-meter walk test (10MWT). The 10MWT is a well-established tool for assessing gait function in stroke patients, evaluating walking speed over short distances. Three measurements were taken for both the patient's usual comfortable walking speed and their maximum walking speed, with mean values calculated. Following the standard procedure, speed was measured in the middle segment, excluding acceleration and deceleration phases. Secondary outcomes included the Timed Up and Go test (TUG), a tool used to evaluate dynamic balance, mobility, and fall risk. The TUG test begins with the participant seated in a chair; it involves standing, walking 3 m, turning around, and returning to the chair. The total time to complete the task was recorded, and the mean of 3 trials was calculated. Additionally, the Berg Balance Scale (BBS) and Functional Ambulation Category, commonly used for functional assessment in stroke patients, were assessed. The Modified Barthel Index was used to evaluate the performance of activities of daily living, and the EQ-5D-3L was used to assess quality of life. Outcome assessments were conducted at 3 time points: before the intervention (T0), after the 12 sessions of the intervention (T1), and 8 weeks after the completion of the intervention (T2) (Fig. 1 ). These assessments were carried out by trained therapists who remained blinded to group allocations. Patients received 12 sessions of transcranial direct current stimulation or sham stimulation during gait training. Outcome assessments were performed at 3 time points. Statistical Analysis Fisher's exact test was used for categorical variables, while the Mann-Whitney U test was employed for continuous and ordinal variables to compare demographics and baseline characteristics between the GtDCS and Gsham groups. Owing to the small sample size, nonparametric tests were used for analysis. Changes in outcome variables over time in the GtDCS and Gsham groups were analyzed using repeated-measures ANOVA (analysis of variance). Subgroup analyses were conducted for patients whose MEPs were induced by TMS. All statistical analyses were performed using SPSS Statistics for Windows, version 27.0.0.0 (IBM Corp., Armonk, NY, USA). A p-value less than 0.05 was considered statistically significant. Results Twenty-six patients were initially assessed for eligibility, and 20 were subsequently enrolled in the study (Fig. 2 ). One patient from the GtDCS group and 2 from the Gsham group dropped out during the intervention. Furthermore, 3 patients from the GtDCS group and 6 from the Gsham group were lost to follow-up at the time of the final assessment (T2). There were no significant differences in demographic characteristics and baseline assessment results between the 2 groups (Table 1 ). Six patients in each group exhibited MEPs in the hemiparetic tibialis anterior muscle. Motor cortex locations responsible for tibialis anterior muscle activity in each patient are presented in Table 2 . Table 1 Demographic Characteristics and Results of Baseline Assessment Total (n = 17) GtDCS (n = 9) Gsham (n = 8) P -value Age, y 61.71 ± 11.77 65.78 ± 12.60 57.13 ± 9.49 0.093 Sex, n (men/women) 10/7 5/4 5/3 1.000 Side of hemiplegia, n (right/left) 8/9 3/6 5/3 0.347 Diabetes mellitus, n 3 3 0 0.206 Hypertension, n 11 6 5 1.000 MEP on hemiparetic leg, n (induced/ not induced) 12/5 6/3 6/2 1.000 Body mass index, kg·m -2 26.51 ± 4.11 25.45 ± 2.50 27.71 ± 5.32 0.673 10-meter walk test, m·s -1 Comfortable speed 0.687 ± 0.227 0.619 ± 0.243 0.762 ± 0.194 0.321 Maximal speed 0.826 ± 0.265 0.755 ± 0.291 0.904 ± 0.223 0.200 Timed up and go test, s 11.5 ± 3.8 12.2 ± 3.8 10.7 ± 4.0 0.481 Berg balance scale 36.06 ± 7.96 32.11 ± 4.78 40.50 ± 8.72 0.074 Functional ambulation category 3.52 ± 0.80 3.33 ± 0.71 3.75 ± 0.89 0.277 Modified Barthel index 76.41 ± 10.40 73.56 ± 10.05 79.62 ± 10.47 0.277 EQ-5D-3L 8.53 ± 1.97 8.33 ± 2.18 8.75 ± 1.83 0.888 MEP indicates motor-evoked potential. Table 2 Estimated Location of the Motor Cortex of the Tibialis Anterior Muscle ID Sex Age Horizontal (cm) + Vertical (cm) † Pt 1 F 81 + 5 + 2 Pt 2 M 64 NR NR Pt 3 M 62 -2 + 3 Pt 4 M 75 + 3 -2 Pt 5 M 70 + 4 -5 Pt 6 F 42 NR NR Pt 7 F 74 -4 -2 Pt 9 M 72 + 9 -2 Pt 10 M 72 NR NR Pt 11 M 67 -4 -3 Pt 12 M 59 NR NR Pt 15 M 51 -2 + 2 Pt 16 F 47 + 7 -3 Pt 17 M 58 -4 + 4 Pt 18 F 61 + 3 + 1 Pt 19 F 43 -3 + 2 Pt 20 F 51 + 3 + 1 Pt indicates patient; and NR, non-response. *Horizontal distance from Cz; positive values indicate the right direction. †Vertical distance from Cz; positive values indicate the anterior direction. No significant differences were found in the 10MWT results between the GtDCS and Gsham groups (Table 3 ). In contrast, the GtDCS group showed significant improvement in BBS scores throughout the intervention (P = 0.001). Table 3 Primary and Secondary Outcomes Throughout the Intervention Group T0 T1 T2 Time effect * Time·Group effect * Primary outcome 10-meter walk test, m·s -1 Comfortable speed GtDCS 0.619 ± 0.243 0.653 ± 0.237 0.726 ± 0.286 0.054 0.381 Gsham 0.762 ± 0.194 0.706 ± 0.165 0.925 ± 0.107 0.118 Maximal speed GtDCS 0.755 ± 0.291 0.819 ± 0.306 0.872 ± 0.318 0.278 0.444 Gsham 0.904 ± 0.223 0.886 ± 0.251 1.006 ± 0.076 0.269 Secondary outcomes Timed up and go test, s GtDCS 12.2 ± 3.8 11.8 ± 4.3 11.5 ± 5.7 0.841 0.480 Gsham 10.7 ± 4.0 10.5 ± 3.9 8.1 ± 0.6 0.658 Berg balance scale GtDCS 32.11 ± 4.78 33.56 ± 4.88 34.17 ± 4.70 0.001 † 0.034 † Gsham 40.50 ± 8.72 41.00 ± 8.00 39.00 ± 11.31 0.546 Functional ambulation category GtDCS 3.33 ± 0.71 3.56 ± 0.73 3.67 ± 0.52 0.051 0.434 Gsham 3.75 ± 0.89 3.75 ± 0.71 4.00 ± 0.00 0.410 Modified Barthel index GtDCS 73.56 ± 10.05 76.78 ± 7.61 78.17 ± 8.70 0.054 0.417 Gsham 79.62 ± 10.47 80.50 ± 11.10 72.50 ± 16.26 0.147 EQ-5D-3L GtDCS 8.33 ± 2.18 7.33 ± 2.24 8.50 ± 2.07 0.346 0.310 Gsham 8.75 ± 1.83 8.88 ± 1.80 9.00 ± 2.82 0.915 *Time effect and time·group effect are shown as P-values. †significant results (P < 0.05). In the subgroup analysis of patients with elicited MEPs, there was improvement not only in BBS scores but also in 10MWT results at a comfortable pace within the GtDCS group (P = 0.031) (Table 4 ). Table 4 Primary and Secondary Outcomes of Subgroup Analyses for Patients With Elicited Motor-Evoked Potentials Group T0 T1. T2 Time effect * Time·Group effect * Primary outcome 10-meter walk test, m·s -1 Comfortable speed GtDCS 0.689 ± 0.247 0.742 ± 0.214 0.837 ± 0.241 0.031 † 0.929 Gsham 0.746 ± 0.225 0.706 ± 0.195 - 0.552 Maximal speed GtDCS 0.857 ± 0.289 0.952 ± 0.255 1.003 ± 0.236 0.306 0.840 Gsham 0.884 ± 0.258 0.893 ± 0.295 - 0.820 Secondary outcomes Timed up and go test, s GtDCS 11.0 ± 3.5 10.1 ± 3.2 9.3 ± 2.8 0.093 0.689 Gsham 11.5 ± 4.5 11.0 ± 4.4 - 0.463 Berg balance scale GtDCS 32.50 ± 4.76 33.83 ± 4.26 35.75 ± 4.57 0.005 † 0.051 Gsham 41.67 ± 7.74 42.17 ± 8.42 - 0.581 Functional ambulation category GtDCS 3.50 ± 0.55 3.83 ± 0.41 3.75 ± 0.50 0.212 0.711 Gsham 3.83 ± 0.98 3.83 ± 0.75 - 1.000 Modified Barthel index GtDCS 77.17 ± 8.89 79.50 ± 6.66 81.50 ± 5.80 0.128 0.434 Gsham 82.50 ± 8.60 83.17 ± 9.24 - 0.175 EQ-5D-3L GtDCS 8.33 ± 2.07 6.83 ± 1.94 8.00 ± 2.45 0.339 0.312 Gsham 8.83 ± 1.47 8.50 ± 1.87 - 0.363 *Time effect and time·group effect are shown as P-values. †significant results (P < 0.05). Discussion In this pilot clinical trial, simultaneous tDCS during gait training was not associated with a statistically significant improvement in walking speed, as measured by the 10MWT, among chronic stroke patients. However, patients who underwent simultaneous tDCS and gait training demonstrated an improvement in balance. These effects were not only observed immediately after the intervention but also persisted 2 months later. A systematic review conducted by Mitsutake et al. (2021) revealed that the effect of overall anodal tDCS was not significantly different from that of sham tDCS [ 6 ]. However, online stimulation, where tDCS and gait training were performed simultaneously, improved walking speed significantly relative to sham tDCS. This concurrent gait training with tDCS may enhance the plasticity of neural networks by facilitating learning mechanisms and ultimately result in improved gait performance. It is important to note that in certain studies where simultaneous tDCS was combined with robot-assisted gait training or high-intensity interval training, no additional beneficial effects were observed in terms of gait performance improvement [ 7 , 8 ]. Notably, these studies employed relatively lower intensities of tDCS, specifically at 1.0 mA or 1.5 mA. The motor cortex responsible for the lower limb lies relatively deeper within the interhemispheric fissure compared with the motor cortex responsible for the upper limb. This anatomical difference may require a higher intensity of tDCS for effective delivery of electrical current to the lower limb motor cortex [ 9 ]. Therefore, it can be inferred that to enhance the efficacy of gait training through tDCS, effective delivery of electrical current to the motor cortex responsible for the lower limb is crucial. Furthermore, stroke induces changes in the distribution of sensory and motor representations within the brain [ 10 ]. This involves the emergence of new patterns of cortical connections within damaged brain areas. Considering such cortical remapping, we hypothesized that precise, targeted delivery of electrical current to the target cortex may maximize motor recovery following tDCS. In most prior studies, electrical stimulation was typically administered at the C3/C4 position according to the 10–20 system, recognized as the primary motor area for the lower limb [ 6 ]. However, it is important to consider that the location of the area responsible for the lower limb may shift due to cortical remapping processes following a stroke [ 10 ]. In our study, when we recorded the estimated locations of the tibialis anterior area within the precentral gyrus through MEPs, we observed significant variability among individual patients (Table 2 ). Therefore, in contrast to the conventional method of merely attaching the anode to the C3/C4 position, we attempted “targeted stimulation” by attaching the anode to the motor area of the tibialis anterior confirmed through MEP, following Chang's method [ 4 ]. Subgroup analysis conducted on patients who underwent “targeted” tDCS on the precentral gyrus of the lower limb revealed a noticeable improvement in walking speed. Our protocol, which precisely targeted the motor cortex and delivered electrical currents with a sufficient intensity of 2.0 mA, might have contributed to inducing appropriate cortical modulation and the subsequent improvement in balance and walking speed among chronic stroke patients. These findings underscore the importance of individualized approaches in tDCS protocols for stroke rehabilitation. In the domain of another non-invasive brain stimulation technique, repetitive TMS, a recent development involves the use of a navigation method by functional near-infrared spectroscopy (fNIRS) [ 11 ]. The fNIRS-aided navigation method exhibits excellent sensitivity and topographical resolution compared with the conventional MEP-guided method [ 12 ]. The enhanced sensitivity and topographical resolution of fNIRS may facilitate a more significant therapeutic effect than protocols guided by MEPs. Additionally, even in patients where MEPs are not elicited for various reasons, fNIRS has been used to facilitate hotspot localization. Thus, non-invasive brain stimulation techniques are trending toward using navigation methods to deliver precise and targeted stimulation. In this study, there were patients who could not undergo targeted tDCS because their MEPs were not elicited. However, the introduction of an fNIRS-guided protocol may overcome such limitations. In the subgroup analysis of patients with elicited MEPs, improvements in walking speed were observed when individuals were instructed to walk at their usual, comfortable pace. It is noteworthy that although there were no improvements in the 10MWT performed at maximum, there were improvements observed when patients walked at a comfortable speed. Postural imbalance resulting from a stroke is a contributing factor to the deterioration of walking capacity [ 13 ]. In this study, it is hypothesized that the improvement of balance through tDCS is likely to be reflected in enhanced gait stability and improved walking speed. There were several limitations to this study. First, this was a pilot study with a small sample size. In the future, larger confirmatory research is required to establish the validity of concurrent tDCS during gait training. Second, the study aimed to assess the long-term effects of simultaneous tDCS during gait training; however, a significant number of patients dropped out during the study due to the COVID-19 pandemic. Third, the study was initially designed to compare a simultaneous tDCS protocol with a sham group. However, additional subgroup analysis suggested the feasibility of a targeted tDCS protocol. Further research, including a non-targeted simultaneous tDCS group, is needed to evaluate the efficacy of a targeted tDCS protocol. Fourth, improvements in gait performance were noted in some patients in this study, but gait analysis was not conducted. It would be beneficial to analyze changes in certain spatiotemporal parameters to understand the detailed effects of tDCS on gait. In conclusion, simultaneous tDCS during gait training did not have a significant impact on the walking speeds of chronic stroke patients in this study. However, the protocol did contribute to improvements in balance. Furthermore, this study suggests the potential of a targeted tDCS protocol to be employed as a novel rehabilitative technique for gait dysfunction caused by stroke. Abbreviations tDCS: transcranial Direct Current Stimulation MEP: Motor-Evoked Potentials TMS: Transcranial Magnetic Stimulation ANOVA: Analysis of Variance 10MWT: 10-Meter Walk Test TUG: Timed Up and Go test BBS: Berg Balance Scale fNIRS: functional Near-Infrared Spectroscopy Declarations Ethics approval and consent to participate The study was approved by the Medical Research Ethics Committee of Chonnam National University Hospital. All participants have provided written consent before participation. Consent for publication The authors verify that consent for publication has been obtained from all participants for individual data presented in this manuscript. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study was supported by CNUH-GIST research collaboration grant [grant number: 2023-0890-01] funded by the Chonnam National University Hospital Biomedical Research Institute. Authors' contributions HM Kim investigated clinical data and contributed to the writing of the original draft. JM Na, HS Jo, MK Song, HK Park, IS Choi, and JW Yoon investigated clinical data and reviewed and edited the original draft. JY Han supervised the study. All authors read and approved the final manuscript. Acknowledgements The authors sincerely thank all the participants for agreeing to participate in this research. We also wish to express profound gratitude to our research team members for their dedication and collaborative spirit during the COVID-19 pandemic. References Durcan S, Flavin E, Horgan F. Factors associated with community ambulation in chronic stroke. 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Front Neurol . 2022;13:690048. https://doi.org/10.3389/fneur.2022.690048 PMID:35222235 Chang PW, Lu CF, Chang ST, Tsai PY. Functional near-infrared spectroscopy as a target navigator for rTMS modulation in patients with hemiplegia: a randomized control study. Neurol Ther . 2022;11:103-121. https://doi.org/10.1007/s40120-021-00300-0 PMID:34773596 Vive S, Elam C, Bunketorp-Käll L. Comfortable and maximum gait speed in individuals with chronic stroke and community-dwelling controls. J Stroke Cerebrovasc Dis . 2021;30:106023. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106023 PMID:34375858 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4173477","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":284348446,"identity":"cb983f7e-8352-4d1c-bcd3-ce9d15a484e7","order_by":0,"name":"Hyeong-Min Kim","email":"","orcid":"","institution":"Chonnam National University Medical School \u0026 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hyeong-Min","middleName":"","lastName":"Kim","suffix":""},{"id":284348449,"identity":"d5da9a37-86b6-457c-bde4-4cb971bf6756","order_by":1,"name":"Ji-Min Na","email":"","orcid":"","institution":"Chonnam National University Medical School \u0026 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ji-Min","middleName":"","lastName":"Na","suffix":""},{"id":284348452,"identity":"dfb201d6-ea51-4783-ad46-fa8fe1895272","order_by":2,"name":"Hyun-Seok Jo","email":"","orcid":"","institution":"Chonnam National University Medical School \u0026 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hyun-Seok","middleName":"","lastName":"Jo","suffix":""},{"id":284348454,"identity":"e6a14c8a-54cd-467b-a157-47e19001e79c","order_by":3,"name":"Min-Keun Song","email":"","orcid":"","institution":"Chonnam National University Medical School \u0026 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Min-Keun","middleName":"","lastName":"Song","suffix":""},{"id":284348455,"identity":"6484c422-4b2b-445f-96e5-00991059e061","order_by":4,"name":"Hyeng-Kyu Park","email":"","orcid":"","institution":"Chonnam National University Medical School \u0026 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hyeng-Kyu","middleName":"","lastName":"Park","suffix":""},{"id":284348456,"identity":"8231a861-6e15-4673-8439-2bd57692abd3","order_by":5,"name":"In-Sung Choi","email":"","orcid":"","institution":"Chonnam National University Medical School \u0026 Hospital","correspondingAuthor":false,"prefix":"","firstName":"In-Sung","middleName":"","lastName":"Choi","suffix":""},{"id":284348457,"identity":"323ff852-52da-42c1-8295-fe9ce4bb7252","order_by":6,"name":"Jungwon Yoon","email":"","orcid":"","institution":"Gwangju Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jungwon","middleName":"","lastName":"Yoon","suffix":""},{"id":284348458,"identity":"7870b2bd-e813-40d4-945e-2080203e2dc5","order_by":7,"name":"Jae-Young Han","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAs0lEQVRIiWNgGAWjYFACHjCWYzhAqhZjmBYJIrUwMCQ2EK3FfNrZg58LZA6n9x0/Y7qBcYdNHUEtMrfzkqVn8BzOnXkmx+wG45k0wrZISOcYSPMAtWw4ANLSdpgoLca/gVrSDc6/AWn5T5QWM5AtCQY3wLYcIE6LNQ9PuuHMG8/KbiS2JUs2EOOw27w91vJ855O33fjYZsdP0BYwYOxphjASiFMPAj8Ix8YoGAWjYBSMYAAAbzg6zUT360YAAAAASUVORK5CYII=","orcid":"","institution":"Chonnam National University Medical School \u0026 Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jae-Young","middleName":"","lastName":"Han","suffix":""}],"badges":[],"createdAt":"2024-03-27 04:59:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4173477/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4173477/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53757874,"identity":"d666442e-1ae5-4fed-b49a-3813d860070d","added_by":"auto","created_at":"2024-03-29 19:09:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22474,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4173477/v1/a1230193a6e9bf325e7cbbcb.png"},{"id":53757873,"identity":"a9a18024-457d-4311-84ff-0318920efad8","added_by":"auto","created_at":"2024-03-29 19:09:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58686,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT (Consolidated Standards of Reporting Trials) flow diagram\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4173477/v1/5c8fd68f4a0ff1f6019252d0.png"},{"id":56208982,"identity":"5ff442c6-e9e9-4917-8a0f-c2f20d22f3d8","added_by":"auto","created_at":"2024-05-10 00:26:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":742981,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4173477/v1/8d68c34c-c024-49d3-98bd-ec109ff3bf99.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Feasibility of Simultaneous Transcranial Direct Current Stimulation During Gait Training in Chronic Stroke Patients: A Randomized Double-blind Pilot Clinical Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImpairment of independent gait is one of the most disabling consequences after a stroke [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Gait abnormality in stroke patients arises from a complex interplay of factors, including lower limb motor weakness and decreased balance. Some individuals may not be entirely incapable of walking, but they may still require gait aids or assistance from caregivers. Gait disturbances pose a greater risk of further injury due to falls. It is well known that fall-associated fractures result in significant socioeconomic costs [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Additionally, gait disturbances lead to limitations in social activity, thereby reducing the quality of life of stroke patients. Therefore, improving gait performance in stroke patients has long been a desire shared by patients and physicians.\u003c/p\u003e \u003cp\u003eTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that aims to modulate the human brain by delivering low-intensity electrical current through the scalp. The mechanism of tDCS is explained by 2 principles: (1) the enhancement of cortical activity through a polarity shift in the resting membrane potential and (2) the upregulation of neural plasticity through long-term potentiation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Applying anodal tDCS to patients with subacute stroke has been associated with beneficial effects on motor function [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, inconsistent results have emerged across studies, with some failing to observe significant improvements in patients who underwent tDCS compared to sham stimulation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Additionally, there has been substantial variability in factors, such as stimulation area, intensity, duration, and the number of sessions among different tDCS protocols, highlighting the need for further research to establish an optimal tDCS protocol for maximizing the effect of conventional gait training methods. Studies focusing on stimulation timing suggest that combining tDCS with gait training simultaneously shows more promising results in improving gait performance compared to protocols that administer gait training and tDCS separately [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aimed to evaluate the feasibility of a rehabilitation protocol that combines simultaneous tDCS with conventional gait training and to investigate its impact on gait performance in chronic stroke patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis was a randomized, double-blind, single-center pilot clinical trial. We prospectively enrolled chronic stroke patients who visited the Department of Physical and Rehabilitation Medicine at Chonnam National University Hospital (Gwangju City, Korea) in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. Written informed consent was obtained from all participants before study enrollment. The study protocol was approved by the Medical Research Ethics Committee of Chonnam National University Hospital, adhering to the principles defined in the Declaration of Helsinki (1964).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eThe inclusion criteria were as follows: (1) patients aged 20 to 90 years; (2) ischemic stroke more than 3 months from onset; (3) unilateral hemiplegia at the time of evaluation; and (4) a functional ambulatory category grade between 2 and 4. The exclusion criteria were (1) diagnosis or concomitant hemorrhagic stroke; (2) gait disturbance resulting from other neurodegenerative, neuromuscular, or musculoskeletal conditions; (3) contraindications to electrostimulation, such as metallic implants in the head, craniectomy status, ongoing treatment for epilepsy, pregnancy, and malignancy; and (4) serious medical conditions that lead to unstable vital signs.\u003c/p\u003e \u003cp\u003eAll eligible patients were randomly assigned to 2 groups: (1) the experimental group, receiving gait training with tDCS (GtDCS), or (2) the control group, receiving gait training with sham stimulation (Gsham).\u003c/p\u003e \u003cp\u003eSimple randomization method was adopted, and random allocation software 2.0 program used to generate the random allocation sequence. This study blinded the participants, outcome evaluator. The outcome evaluator is not allowed to contact the participants and clinical trial coordinator who manages the treatment except during the evaluation period\u003c/p\u003e \u003cp\u003e \u003cb\u003eProcedures\u003c/b\u003e \u003c/p\u003e \u003cp\u003e1) Electrode Placement Configuration\u003c/p\u003e \u003cp\u003eWe identified the appropriate scalp area for attaching electrodes to effectively deliver electrical stimulation to the target cerebral cortical area. To locate the position of the primary motor cortex responsible for leg movement, we recorded motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) at the hemiparetic tibialis anterior muscle. Magstim Rapid2\u0026reg; (Magstim Company Ltd., Whitland, UK) with a 9-cm circular coil was used to perform TMS.\u003c/p\u003e \u003cp\u003eAccording to the international 10\u0026ndash;20 system, Cz was set as the reference point on the patient's scalp. The magnetic stimulation was conducted four times at each site with 1-cm intervals toward the affected cortex from Cz. The stimulation intensity was applied at 100% of the maximum output of the TMS device. During stimulation, the location where the peak-to-peak amplitude of the MEP was greatest was assumed to be the tibialis anterior area of the precentral gyrus. The horizontal and vertical distances from Cz to this point were recorded. MEP recordings through TMS were conducted by a blinded examiner who was unaware of the patient's clinical information.\u003c/p\u003e \u003cp\u003e2) tDCS Application\u003c/p\u003e \u003cp\u003eThe HDCstim\u0026reg; (Newronika, Milan, Italy) device and two saline-soaked sponge surface electrodes, each measuring 25 cm\u003csup\u003e2\u003c/sup\u003e, were used to deliver the electrical current. The center of the anodal electrode was placed above the tibialis anterior area of the precentral gyrus, as confirmed by the MEP evaluation. If MEPs were not induced, the anodal electrode was placed above C3 or C4 according to the international 10\u0026ndash;20 system. The cathodal electrode was positioned on the contralateral supraorbital area.\u003c/p\u003e \u003cp\u003eIn the GtDCS group, patients received tDCS at an intensity of 2.0 mA for 20 minutes during gait training. In the Gsham group, no electrical current was delivered, except for sham stimulation lasting 15 seconds at the beginning and end of the gait training session. During sham stimulation, the stimulator remained operating, rendering it impossible for participants to discern whether they were receiving true brain stimulation.\u003c/p\u003e \u003cp\u003e3) Gait Training\u003c/p\u003e \u003cp\u003eAll patients participated in the gait training program, which consisted of 10 minutes of simple gait training and 10 minutes of complex gait training. The simple gait training involved walking on flat ground, while the complex gait training included activities such as stair climbing, sideways walking, and walking backward. Individuals for whom complex gait training was deemed infeasible due to impaired gait performance engaged in 20 minutes of simple gait training. Assistive walking devices were used as needed during the sessions. The entire training process was conducted under the supervision and assistance of skilled physical therapists, who remained blinded to the patients\u0026rsquo; group allocations.\u003c/p\u003e \u003cp\u003eThe intervention, including gait training and tDCS, was carried out over 12 sessions: 3 times a week for 4 weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome measure was the 10-meter walk test (10MWT). The 10MWT is a well-established tool for assessing gait function in stroke patients, evaluating walking speed over short distances. Three measurements were taken for both the patient's usual comfortable walking speed and their maximum walking speed, with mean values calculated. Following the standard procedure, speed was measured in the middle segment, excluding acceleration and deceleration phases.\u003c/p\u003e \u003cp\u003eSecondary outcomes included the Timed Up and Go test (TUG), a tool used to evaluate dynamic balance, mobility, and fall risk. The TUG test begins with the participant seated in a chair; it involves standing, walking 3 m, turning around, and returning to the chair. The total time to complete the task was recorded, and the mean of 3 trials was calculated. Additionally, the Berg Balance Scale (BBS) and Functional Ambulation Category, commonly used for functional assessment in stroke patients, were assessed. The Modified Barthel Index was used to evaluate the performance of activities of daily living, and the EQ-5D-3L was used to assess quality of life.\u003c/p\u003e \u003cp\u003eOutcome assessments were conducted at 3 time points: before the intervention (T0), after the 12 sessions of the intervention (T1), and 8 weeks after the completion of the intervention (T2) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These assessments were carried out by trained therapists who remained blinded to group allocations.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients received 12 sessions of transcranial direct current stimulation or sham stimulation during gait training. Outcome assessments were performed at 3 time points.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eFisher's exact test was used for categorical variables, while the Mann-Whitney U test was employed for continuous and ordinal variables to compare demographics and baseline characteristics between the GtDCS and Gsham groups. Owing to the small sample size, nonparametric tests were used for analysis. Changes in outcome variables over time in the GtDCS and Gsham groups were analyzed using repeated-measures ANOVA (analysis of variance). Subgroup analyses were conducted for patients whose MEPs were induced by TMS. All statistical analyses were performed using SPSS Statistics for Windows, version 27.0.0.0 (IBM Corp., Armonk, NY, USA). A p-value less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTwenty-six patients were initially assessed for eligibility, and 20 were subsequently enrolled in the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). One patient from the GtDCS group and 2 from the Gsham group dropped out during the intervention. Furthermore, 3 patients from the GtDCS group and 6 from the Gsham group were lost to follow-up at the time of the final assessment (T2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere were no significant differences in demographic characteristics and baseline assessment results between the 2 groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Six patients in each group exhibited MEPs in the hemiparetic tibialis anterior muscle. Motor cortex locations responsible for tibialis anterior muscle activity in each patient are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic Characteristics and Results of Baseline Assessment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGtDCS (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGsham (n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.71\u0026thinsp;\u0026plusmn;\u0026thinsp;11.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.78\u0026thinsp;\u0026plusmn;\u0026thinsp;12.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.13\u0026thinsp;\u0026plusmn;\u0026thinsp;9.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (men/women)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSide of hemiplegia, n (right/left)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.347\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.206\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMEP on hemiparetic leg, n (induced/ not induced)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index, kg\u0026middot;m\u003csup\u003e-2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.51\u0026thinsp;\u0026plusmn;\u0026thinsp;4.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.45\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.71\u0026thinsp;\u0026plusmn;\u0026thinsp;5.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10-meter walk test, m\u0026middot;s\u003csup\u003e-1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComfortable speed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.687\u0026thinsp;\u0026plusmn;\u0026thinsp;0.227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.619\u0026thinsp;\u0026plusmn;\u0026thinsp;0.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.762\u0026thinsp;\u0026plusmn;\u0026thinsp;0.194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximal speed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.826\u0026thinsp;\u0026plusmn;\u0026thinsp;0.265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.755\u0026thinsp;\u0026plusmn;\u0026thinsp;0.291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.904\u0026thinsp;\u0026plusmn;\u0026thinsp;0.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTimed up and go test, s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.481\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBerg balance scale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.06\u0026thinsp;\u0026plusmn;\u0026thinsp;7.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.11\u0026thinsp;\u0026plusmn;\u0026thinsp;4.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.50\u0026thinsp;\u0026plusmn;\u0026thinsp;8.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFunctional ambulation category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModified Barthel index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.41\u0026thinsp;\u0026plusmn;\u0026thinsp;10.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.56\u0026thinsp;\u0026plusmn;\u0026thinsp;10.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.62\u0026thinsp;\u0026plusmn;\u0026thinsp;10.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEQ-5D-3L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.888\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMEP indicates motor-evoked potential.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEstimated Location of the Motor Cortex of the Tibialis Anterior Muscle\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHorizontal (cm)\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVertical (cm)\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt 20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePt indicates patient; and NR, non-response. *Horizontal distance from Cz; positive values indicate the right direction. \u0026dagger;Vertical distance from Cz; positive values indicate the anterior direction.\u003c/p\u003e \u003cp\u003eNo significant differences were found in the 10MWT results between the GtDCS and Gsham groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In contrast, the GtDCS group showed significant improvement in BBS scores throughout the intervention (P\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary and Secondary Outcomes Throughout the Intervention\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTime effect\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTime\u0026middot;Group effect\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10-meter walk test, m\u0026middot;s\u003csup\u003e-1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComfortable speed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.619\u0026thinsp;\u0026plusmn;\u0026thinsp;0.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.653\u0026thinsp;\u0026plusmn;\u0026thinsp;0.237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.726\u0026thinsp;\u0026plusmn;\u0026thinsp;0.286\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.381\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.762\u0026thinsp;\u0026plusmn;\u0026thinsp;0.194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.706\u0026thinsp;\u0026plusmn;\u0026thinsp;0.165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.925\u0026thinsp;\u0026plusmn;\u0026thinsp;0.107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximal speed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.755\u0026thinsp;\u0026plusmn;\u0026thinsp;0.291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.819\u0026thinsp;\u0026plusmn;\u0026thinsp;0.306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.872\u0026thinsp;\u0026plusmn;\u0026thinsp;0.318\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.278\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.904\u0026thinsp;\u0026plusmn;\u0026thinsp;0.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.886\u0026thinsp;\u0026plusmn;\u0026thinsp;0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.006\u0026thinsp;\u0026plusmn;\u0026thinsp;0.076\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.269\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTimed up and go test, s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e11.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.480\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBerg balance scale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e32.11\u0026thinsp;\u0026plusmn;\u0026thinsp;4.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e33.56\u0026thinsp;\u0026plusmn;\u0026thinsp;4.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e34.17\u0026thinsp;\u0026plusmn;\u0026thinsp;4.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e40.50\u0026thinsp;\u0026plusmn;\u0026thinsp;8.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e41.00\u0026thinsp;\u0026plusmn;\u0026thinsp;8.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e39.00\u0026thinsp;\u0026plusmn;\u0026thinsp;11.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFunctional ambulation\u003c/p\u003e \u003cp\u003ecategory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e3.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e4.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.410\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModified Barthel index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e73.56\u0026thinsp;\u0026plusmn;\u0026thinsp;10.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e76.78\u0026thinsp;\u0026plusmn;\u0026thinsp;7.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e78.17\u0026thinsp;\u0026plusmn;\u0026thinsp;8.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.417\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e79.62\u0026thinsp;\u0026plusmn;\u0026thinsp;10.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e80.50\u0026thinsp;\u0026plusmn;\u0026thinsp;11.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e72.50\u0026thinsp;\u0026plusmn;\u0026thinsp;16.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEQ-5D-3L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e7.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e8.50\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.310\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e9.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.915\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Time effect and time\u0026middot;group effect are shown as P-values. \u0026dagger;significant results (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eIn the subgroup analysis of patients with elicited MEPs, there was improvement not only in BBS scores but also in 10MWT results at a comfortable pace within the GtDCS group (P\u0026thinsp;=\u0026thinsp;0.031) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary and Secondary Outcomes of Subgroup Analyses for Patients With Elicited Motor-Evoked Potentials\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT1.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTime effect\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTime\u0026middot;Group effect\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10-meter walk test, m\u0026middot;s\u003csup\u003e-1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComfortable speed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.689\u0026thinsp;\u0026plusmn;\u0026thinsp;0.247\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.742\u0026thinsp;\u0026plusmn;\u0026thinsp;0.214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.837\u0026thinsp;\u0026plusmn;\u0026thinsp;0.241\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.031\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.746\u0026thinsp;\u0026plusmn;\u0026thinsp;0.225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.706\u0026thinsp;\u0026plusmn;\u0026thinsp;0.195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.552\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximal speed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.857\u0026thinsp;\u0026plusmn;\u0026thinsp;0.289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.952\u0026thinsp;\u0026plusmn;\u0026thinsp;0.255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.003\u0026thinsp;\u0026plusmn;\u0026thinsp;0.236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.840\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.884\u0026thinsp;\u0026plusmn;\u0026thinsp;0.258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.893\u0026thinsp;\u0026plusmn;\u0026thinsp;0.295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.820\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTimed up and go test, s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.689\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.463\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBerg balance scale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e32.50\u0026thinsp;\u0026plusmn;\u0026thinsp;4.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e33.83\u0026thinsp;\u0026plusmn;\u0026thinsp;4.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.75\u0026thinsp;\u0026plusmn;\u0026thinsp;4.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e41.67\u0026thinsp;\u0026plusmn;\u0026thinsp;7.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e42.17\u0026thinsp;\u0026plusmn;\u0026thinsp;8.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.581\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFunctional ambulation\u003c/p\u003e \u003cp\u003ecategory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModified Barthel index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e77.17\u0026thinsp;\u0026plusmn;\u0026thinsp;8.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e79.50\u0026thinsp;\u0026plusmn;\u0026thinsp;6.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e81.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e82.50\u0026thinsp;\u0026plusmn;\u0026thinsp;8.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e83.17\u0026thinsp;\u0026plusmn;\u0026thinsp;9.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEQ-5D-3L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGtDCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.312\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGsham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Time effect and time\u0026middot;group effect are shown as P-values. \u0026dagger;significant results (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this pilot clinical trial, simultaneous tDCS during gait training was not associated with a statistically significant improvement in walking speed, as measured by the 10MWT, among chronic stroke patients. However, patients who underwent simultaneous tDCS and gait training demonstrated an improvement in balance. These effects were not only observed immediately after the intervention but also persisted 2 months later.\u003c/p\u003e \u003cp\u003eA systematic review conducted by Mitsutake et al. (2021) revealed that the effect of overall anodal tDCS was not significantly different from that of sham tDCS [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, online stimulation, where tDCS and gait training were performed simultaneously, improved walking speed significantly relative to sham tDCS. This concurrent gait training with tDCS may enhance the plasticity of neural networks by facilitating learning mechanisms and ultimately result in improved gait performance.\u003c/p\u003e \u003cp\u003eIt is important to note that in certain studies where simultaneous tDCS was combined with robot-assisted gait training or high-intensity interval training, no additional beneficial effects were observed in terms of gait performance improvement [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Notably, these studies employed relatively lower intensities of tDCS, specifically at 1.0 mA or 1.5 mA. The motor cortex responsible for the lower limb lies relatively deeper within the interhemispheric fissure compared with the motor cortex responsible for the upper limb. This anatomical difference may require a higher intensity of tDCS for effective delivery of electrical current to the lower limb motor cortex [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, it can be inferred that to enhance the efficacy of gait training through tDCS, effective delivery of electrical current to the motor cortex responsible for the lower limb is crucial.\u003c/p\u003e \u003cp\u003eFurthermore, stroke induces changes in the distribution of sensory and motor representations within the brain [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This involves the emergence of new patterns of cortical connections within damaged brain areas. Considering such cortical remapping, we hypothesized that precise, targeted delivery of electrical current to the target cortex may maximize motor recovery following tDCS. In most prior studies, electrical stimulation was typically administered at the C3/C4 position according to the 10\u0026ndash;20 system, recognized as the primary motor area for the lower limb [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, it is important to consider that the location of the area responsible for the lower limb may shift due to cortical remapping processes following a stroke [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our study, when we recorded the estimated locations of the tibialis anterior area within the precentral gyrus through MEPs, we observed significant variability among individual patients (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Therefore, in contrast to the conventional method of merely attaching the anode to the C3/C4 position, we attempted \u0026ldquo;targeted stimulation\u0026rdquo; by attaching the anode to the motor area of the tibialis anterior confirmed through MEP, following Chang's method [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Subgroup analysis conducted on patients who underwent \u0026ldquo;targeted\u0026rdquo; tDCS on the precentral gyrus of the lower limb revealed a noticeable improvement in walking speed. Our protocol, which precisely targeted the motor cortex and delivered electrical currents with a sufficient intensity of 2.0 mA, might have contributed to inducing appropriate cortical modulation and the subsequent improvement in balance and walking speed among chronic stroke patients. These findings underscore the importance of individualized approaches in tDCS protocols for stroke rehabilitation.\u003c/p\u003e \u003cp\u003eIn the domain of another non-invasive brain stimulation technique, repetitive TMS, a recent development involves the use of a navigation method by functional near-infrared spectroscopy (fNIRS) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The fNIRS-aided navigation method exhibits excellent sensitivity and topographical resolution compared with the conventional MEP-guided method [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The enhanced sensitivity and topographical resolution of fNIRS may facilitate a more significant therapeutic effect than protocols guided by MEPs. Additionally, even in patients where MEPs are not elicited for various reasons, fNIRS has been used to facilitate hotspot localization. Thus, non-invasive brain stimulation techniques are trending toward using navigation methods to deliver precise and targeted stimulation. In this study, there were patients who could not undergo targeted tDCS because their MEPs were not elicited. However, the introduction of an fNIRS-guided protocol may overcome such limitations.\u003c/p\u003e \u003cp\u003eIn the subgroup analysis of patients with elicited MEPs, improvements in walking speed were observed when individuals were instructed to walk at their usual, comfortable pace. It is noteworthy that although there were no improvements in the 10MWT performed at maximum, there were improvements observed when patients walked at a comfortable speed. Postural imbalance resulting from a stroke is a contributing factor to the deterioration of walking capacity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this study, it is hypothesized that the improvement of balance through tDCS is likely to be reflected in enhanced gait stability and improved walking speed.\u003c/p\u003e \u003cp\u003eThere were several limitations to this study. First, this was a pilot study with a small sample size. In the future, larger confirmatory research is required to establish the validity of concurrent tDCS during gait training. Second, the study aimed to assess the long-term effects of simultaneous tDCS during gait training; however, a significant number of patients dropped out during the study due to the COVID-19 pandemic. Third, the study was initially designed to compare a simultaneous tDCS protocol with a sham group. However, additional subgroup analysis suggested the feasibility of a targeted tDCS protocol. Further research, including a non-targeted simultaneous tDCS group, is needed to evaluate the efficacy of a targeted tDCS protocol. Fourth, improvements in gait performance were noted in some patients in this study, but gait analysis was not conducted. It would be beneficial to analyze changes in certain spatiotemporal parameters to understand the detailed effects of tDCS on gait.\u003c/p\u003e \u003cp\u003eIn conclusion, simultaneous tDCS during gait training did not have a significant impact on the walking speeds of chronic stroke patients in this study. However, the protocol did contribute to improvements in balance. Furthermore, this study suggests the potential of a targeted tDCS protocol to be employed as a novel rehabilitative technique for gait dysfunction caused by stroke.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003etDCS: transcranial Direct Current Stimulation\u003c/p\u003e\n\u003cp\u003eMEP: Motor-Evoked Potentials\u003c/p\u003e\n\u003cp\u003eTMS: Transcranial Magnetic Stimulation\u003c/p\u003e\n\u003cp\u003eANOVA: Analysis of Variance\u003c/p\u003e\n\u003cp\u003e10MWT: 10-Meter Walk Test\u003c/p\u003e\n\u003cp\u003eTUG: Timed Up and Go test\u003c/p\u003e\n\u003cp\u003eBBS: Berg Balance Scale\u0026nbsp;\u003c/p\u003e\n\u003cp\u003efNIRS: functional Near-Infrared Spectroscopy\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Medical Research Ethics Committee of Chonnam National University Hospital. All participants have provided written consent before participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors verify that consent for publication has been obtained from all participants for individual data presented in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by CNUH-GIST research collaboration grant [grant number: 2023-0890-01] funded by the Chonnam National University Hospital Biomedical Research Institute.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHM Kim investigated clinical data and contributed to the writing of the original draft. JM Na, HS Jo, MK Song, HK Park, IS Choi, and JW Yoon investigated clinical data and reviewed and edited the original draft. JY Han supervised the study. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors sincerely thank all the participants for agreeing to participate in this research. We also wish to express profound gratitude to our research team members for their dedication and collaborative spirit during the COVID-19 pandemic.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDurcan S, Flavin E, Horgan F. Factors associated with community ambulation in chronic stroke. \u003cem\u003eDisabil Rehabil\u003c/em\u003e. 2016;38:245-249. https://doi.org/10.3109/09638288.2015.1035460 PMID:25856203\u003c/li\u003e\n\u003cli\u003eJohnson CO, Nguyen M, Roth GA, Nichols E, Alam T, Abate D, Abd-Allah F, Abdelalim A, Niguse Abraha H, Abu-Rmeileh NME, et al; GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. \u003cem\u003eLancet Neurol\u003c/em\u003e. 2019;18:439-458. https://doi.org/10.1016/S1474-4422(19)30034-1 PMID:30871944\u003c/li\u003e\n\u003cli\u003eBrunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, Edwards DJ, Valero-Cabre A, Rotenberg A, Pascual-Leone A, et al. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. \u003cem\u003eBrain Stimul\u003c/em\u003e. 2012;5:175-195. https://doi.org/10.1016/j.brs.2011.03.002 PMID:22037126\u003c/li\u003e\n\u003cli\u003eChang MC, Kim DY, Park DH. Enhancement of Cortical Excitability and Lower Limb Motor Function in Patients With Stroke by Transcranial Direct Current Stimulation. \u003cem\u003eBrain \u003c/em\u003e\u003cem\u003eStimul\u003c/em\u003e. 2015;8:561-566. https://doi.org/10.1016/j.brs.2015.01.411 PMID:25736569\u003c/li\u003e\n\u003cli\u003ede Paz RH, Serrano-Mu\u0026ntilde;oz D, P\u0026eacute;rez-Nombela S, Bravo-Esteban E, Avenda\u0026ntilde;o-Coy J, G\u0026oacute;mez-Soriano J. Combining transcranial direct-current stimulation with gait training in patients with neurological disorders: a systematic review. \u003cem\u003eJ Neuroeng Rehabil\u003c/em\u003e. 2019;16:114. https://doi.org/10.1186/s12984-019-0591-z PMID:31521179\u003c/li\u003e\n\u003cli\u003eMitsutake T, Imura T, Hori T, Sakamoto M, Tanaka R. Effects of Combining Online Anodal Transcranial Direct Current Stimulation and Gait Training in Stroke Patients: A Systematic Review and Meta-Analysis. \u003cem\u003eFront Hum Neurosci\u003c/em\u003e. 2021;15:782305. https://doi.org/10.3389/fnhum.2021.782305 PMID:34955795\u003c/li\u003e\n\u003cli\u003eGeroin 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. \u003cem\u003eClin Rehabil\u003c/em\u003e. 2011;25:537-548. https://doi.org/10.1177/0269215510389497 PMID:21402651\u003c/li\u003e\n\u003cli\u003eMadhavan S, Cleland BT, Sivaramakrishnan A, Freels S, Lim H, Testai FD, Corcos DM. Cortical priming strategies for gait training after stroke: a controlled, stratified trial. \u003cem\u003eJ Neuroeng Rehabil\u003c/em\u003e. 2020;17:111. https://doi.org/10.1186/s12984-020-00744-9 PMID:32799922\u003c/li\u003e\n\u003cli\u003eJeffery DT, Norton JA, Roy FD, Gorassini MA. Effects of transcranial direct current stimulation on the excitability of the leg motor cortex. \u003cem\u003eExp Brain Res\u003c/em\u003e. 2007;182:281-287. https://doi.org/10.1007/s00221-007-1093-y PMID:17717651\u003c/li\u003e\n\u003cli\u003eCarmichael ST. Plasticity of cortical projections after stroke. \u003cem\u003eNeuroscientist\u003c/em\u003e. 2003;9:64-75. https://doi.org/10.1177/1073858402239592 PMID:12580341\u003c/li\u003e\n\u003cli\u003eChang WK, Park J, Lee JY, Cho S, Lee J, Kim WS, Paik NJ. Functional network changes after high-frequency rTMS over the most activated speech-related area combined with speech therapy in chronic stroke with non-fluent aphasia. \u003cem\u003eFront Neurol\u003c/em\u003e. 2022;13:690048. https://doi.org/10.3389/fneur.2022.690048 PMID:35222235\u003c/li\u003e\n\u003cli\u003eChang PW, Lu CF, Chang ST, Tsai PY. Functional near-infrared spectroscopy as a target navigator for rTMS modulation in patients with hemiplegia: a randomized control study. \u003cem\u003eNeurol Ther\u003c/em\u003e. 2022;11:103-121. https://doi.org/10.1007/s40120-021-00300-0 PMID:34773596\u003c/li\u003e\n\u003cli\u003eVive S, Elam C, Bunketorp-K\u0026auml;ll L. Comfortable and maximum gait speed in individuals with chronic stroke and community-dwelling controls. \u003cem\u003eJ Stroke Cerebrovasc Dis\u003c/em\u003e. 2021;30:106023. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106023 PMID:34375858\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"gait disturbance, stroke, rehabilitation, transcranial direct current stimulation","lastPublishedDoi":"10.21203/rs.3.rs-4173477/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4173477/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTranscranial direct current stimulation (tDCS) is a therapeutic tool for improving post-stroke gait disturbances, with ongoing research focusing on specific protocols for its application. We evaluated the feasibility of a rehabilitation protocol that combines tDCS with conventional gait training.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was a randomized, double-blind, single-center pilot clinical trial. Patients with unilateral hemiplegia due to ischemic stroke were randomly assigned to either the tDCS with gait training group or the sham stimulation group. The anodal tDCS electrode was placed on the tibialis anterior area of the precentral gyrus while gait training proceeded. Interventions were administered 3 times weekly for 4 weeks. Outcome assessments, using the 10-meter walk test, Timed Up and Go test, Berg Balance Scale, Functional Ambulatory Scale, Modified Barthel Index, and EQ-5D-3L, were conducted before and after the intervention and again at the 8-week mark following its completion. Repeated-measures ANOVA was used for comparisons between and within groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwenty-six patients were assessed for eligibility, and 20 were enrolled and randomized. No significant differences were observed between the tDCS with gait training group and the sham stimulation group in gait speed after the intervention. However, the tDCS with gait training group showed significant improvement in balance performance in both within-group and between-group comparisons. In the subgroup analysis of patients with elicited motor-evoked potentials, comfortable pace gait speed improved in the tDCS with gait training group. No serious adverse events occurred throughout the study.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSimultaneous tDCS during gait training is a feasible rehabilitation protocol for chronic stroke patients with gait disturbances.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eURL: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cris.nih.go.kr\u003c/span\u003e\u003cspan address=\"https://cris.nih.go.kr\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e; Registration number: KCT0007601; Date of registration: 11 July 2022\u003c/p\u003e","manuscriptTitle":"Feasibility of Simultaneous Transcranial Direct Current Stimulation During Gait Training in Chronic Stroke Patients: A Randomized Double-blind Pilot Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-29 19:09:44","doi":"10.21203/rs.3.rs-4173477/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3e29233a-e877-4aef-8a1c-bb81c7f0bee6","owner":[],"postedDate":"March 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-10T00:25:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-29 19:09:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4173477","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4173477","identity":"rs-4173477","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}