Motor Recovery In Stroke Patients Research Articles

Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial.

Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Different doses of intermittent theta burst stimulation for upper limb motor dysfunction after stroke: a study protocol for a randomized controlled trial.

Upper limb motor recovery is one of the important goals of stroke rehabilitation. Intermittent theta burst stimulation (iTBS), a new type of repetitive transcranial magnetic stimulation (rTMS), is considered a potential therapy. However, there is still no consensus on the efficacy of iTBS for upper limb motor dysfunction after stroke. Stimulus dose may be an important factor affecting the efficacy of iTBS. Therefore, we aim to investigate and compare the effects and neural mechanisms of three doses of iTBS on upper limb motor recovery in stroke patients, and our hypothesis is that the higher the dose of iTBS, the greater the improvement in upper limb motor function. This prospective, randomized, controlled trial will recruit 56 stroke patients with upper limb motor dysfunction. All participants will be randomized in a 1:1:1:1 ratio to receive 21 sessions of 600 pulses active iTBS, 1,200 pulses active iTBS, 1,800 pulses active iTBS, or 1,800 pulses sham iTBS in addition to conventional rehabilitation training. The primary outcome is the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score from baseline to end of intervention, and the secondary outcomes are the Wolf Motor Function Test (WMFT), Grip Strength (GS), Modified Barthel Index (MBI), and Stroke Impact Scale (SIS). The FMA-UE, MBI, and SIS are assessed pre-treatment, post-treatment, and at the 3-weeks follow-up. The WMFT, GS, and resting-state functional magnetic resonance imaging (rs-fMRI) data will be obtained pre- and post-treatment. The iTBS intervention in this study protocol is expected to be a potential method to promote upper limb motor recovery after stroke, and the results may provide supportive evidence for the optimal dose of iTBS intervention.

Protocol for a single-blind randomized clinical trial to test the efficacy of bilateral transcranial magnetic stimulation on upper extremity motor function in patients recovering from stroke

BackgroundNo consensus currently exists regarding the optimal protocol for repetitive transcranial magnetic stimulation (rTMS) treatment of upper-extremity motor dysfunction after stroke. Studies have shown that combined low- and high-frequency stimulation (LF-HF-rTMS) of the bilateral cerebral hemispheres is more effective than sham stimulation or stimulation of one cerebral hemisphere alone in treating motor dysfunction in the subacute stage of stroke. The efficacy of this protocol in the convalescence phase of stroke has rarely been reported, and its mechanism of action has not been clarified. In this study, we designed a prospective, single-blind, randomized controlled trial to investigate the efficacy and safety of different stimulation regimens for the treatment of upper extremity motor disorders in patients with convalescent stage stroke and aimed to explore the underlying mechanisms based on biomarkers such as brain-derived neurotrophic factor (BDNF).MethodsSeventy-six subjects will be randomly divided into combined, low-frequency, high-frequency, and control groups based on the proportion of 1:1:1:1, with 19 cases in each group. All groups will have conventional rehabilitation, on top of which the combined group will receive 1 Hz rTMS in the unaffected hemisphere and 10 Hz rTMS in the affected hemisphere. The low-frequency group will be administered 1 Hz rTMS in the unaffected hemisphere and sham stimulation in the contralateral hemisphere. The high-frequency group will be administered 10 Hz rTMS in the affected hemisphere and contralateral sham stimulation. The control group will receive bilateral sham stimulation. Assessments will be performed at baseline, after 2 weeks of treatment, and at post-treatment follow-up at week 6. The primary outcomes are FMA-UE (Fugl-Meyer assessment-upper extremity), latency, and serum BDNF levels. The secondary outcomes are the National Institute of Health Stroke Scale (NIHSS), Brunnstrom staging (BS), modified Ashworth scale (MAS), Modified Barthel Index (MBI), central motor conduction time (CMCT), precursor proteins of mature BDNF (proBDNF), and matrix metalloproteinase-9 (MMP-9) levels. Adverse events, such as headaches and seizures, will be recorded throughout the study.DiscussionThe findings of this study will help develop optimal stimulation protocols for motor recovery in stroke patients and identify biomarkers that respond to post-stroke motor rehabilitation, for better guidance of clinical treatment.Trial registrationThe study protocol was passed by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 1, 2022 (no. KYLL-2021–1082). It was registered into the Chinese Clinical Trials Registry on May 22, 2022 (no. ChiCTR2200060201). This study is currently in progress.Graphical

A Method for Using Video Presentation to Increase Cortical Region Activity during Motor Imagery Tasks in Stroke Patients.

Previous studies have reported that stroke patients have difficulty recalling the motor imagery (MI) of a task, also known as MI vividness. Research on combining MI with action observation is gaining importance as a method to improve MI vividness. We enrolled 10 right-handed stroke patients and compared MI vividness and cortical activity under different presentation methods (no inverted image, inverted image of another individual's hand, and an inverted image of the patient's nonparalyzed hand) using near-infrared spectroscopy. Images of the nonparalyzed upper limb were inverted to make the paralyzed upper limb appear as if it were moving. Three tasks (non inverted image, AO + MI (other hand), AO + MI (own hand)) were randomly performed on 10 stroke patients. MI vividness was significantly higher when the inverted image of the nonparalyzed upper limb was presented compared to the other conditions (p < 0.01). The activity of the cortical regions was also significantly enhanced (p < 0.01). Our study highlights the potential application of inverted images of a stroke patient's own nonparalyzed hand in mental practice to promote the motor recovery of stroke patients. This technique achieved higher levels of MI vividness and cortical activity when performing motor tasks.

Repetitive Transcranial Magnetic Stimulation Induces Quantified Functional and Structural Changes in Subcortical Stroke: A Combined Arterial Spin Labeling Perfusion and Diffusion Tensor Imaging Study.

PurposeTo explore the changes of cerebral blood flow (CBF) and fractional anisotropy (FA) in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation (rTMS) treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level.Materials and MethodsIn total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls (HCs) were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural MRI were performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales.ResultsAfter rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex (CPC) loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment (FMA) scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract (CST). The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus.ConclusionOur results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST.

Practical Machine Learning Model to Predict the Recovery of Motor Function in Patients with Stroke

Background: Machine learning (ML) is an artificial intelligence technique in which a system learns patterns and rules from a given data. Objectives: The objective of the study was to investigate the potential of ML for predicting motor recovery in stroke patients. Methods: We analyzed data from 833 consecutive stroke patients using 3 ML algorithms: deep neural network (DNN), random forest, and logistic regression. We created a practical ML model using the most common data measured in almost all rehabilitation hospitals as input data. Demographic and clinical data, including modified Brunnstrom classification (MBC) and functional ambulation classification (FAC), were collected when patients were transferred to the rehabilitation unit (8–30 days) and 6 months after stroke onset and were used as input data. Motor outcomes at 6 months after stroke onset of the affected upper and lower extremities were classified according to MBC and FAC, respectively. Patients with an MBC of <5 and an FAC of <4 at 6 months after stroke onset were considered to have a “poor” outcome, whereas those with MBC ≥5 and FAC ≥4 were considered to have a “good” outcome. Results: The area under the curve (AUC) for the DNN model for predicting motor function was 0.836 for the upper and lower limb motor functions. For the random forest and logistic regression models, the AUCs were 0.736 and 0.790 for the upper and lower limb motor functions, respectively. The AUCs for the random forest and logistic regression models were 0.741 and 0.795 for the upper and lower limb motor functions, respectively. Conclusion: Although we used simple and common data that can be obtained in clinical practice as variables, our DNN algorithm was useful for predicting motor recovery of the upper and lower extremities in stroke patients during the recovery phase.

Predicting Individual Treatment Response to rTMS for Motor Recovery After Stroke: A Review and the CanStim Perspective.

BackgroundRehabilitation is critical for reducing stroke-related disability and improving quality-of-life post-stroke. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique used as stand-alone or adjunct treatment to physiotherapy, may be of benefit for motor recovery in subgroups of stroke patients. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) seeks to advance the use of these techniques to improve post-stroke recovery through clinical trials and pre-clinical studies using standardized research protocols. Here, we review existing clinical trials for demographic, clinical, and neurobiological factors which may predict treatment response to identify knowledge gaps which need to be addressed before implementing these parameters for patient stratification in clinical trial protocols.ObjectiveTo provide a review of clinical rTMS trials of stroke recovery identifying factors associated with rTMS response in stroke patients with motor deficits and develop research perspectives for pre-clinical and clinical studies.MethodsA literature search was performed in PubMed, using the Boolean search terms stroke AND repetitive transcranial magnetic stimulation OR rTMS AND motor for studies investigating the use of rTMS for motor recovery in stroke patients at any recovery phase. A total of 1,676 articles were screened by two blinded raters, with 26 papers identified for inclusion in this review.ResultsMultiple possible factors associated with rTMS response were identified, including stroke location, cortical thickness, brain-derived neurotrophic factor (BDNF) genotype, initial stroke severity, and several imaging and clinical factors associated with a relatively preserved functional motor network of the ipsilesional hemisphere. Age, sex, and time post-stroke were generally not related to rTMS response. Factors associated with greater response were identified in studies of both excitatory ipsilesional and inhibitory contralesional rTMS. Heterogeneous study designs and contradictory data exemplify the need for greater protocol standardization and high-quality controlled trials.ConclusionClinical, brain structural and neurobiological factors have been identified as potential predictors for rTMS response in stroke patients with motor impairment. These factors can inform the design of future clinical trials, before being considered for optimization of individual rehabilitation therapy for stroke patients. Pre-clinical models for stroke recovery, specifically developed in a clinical context, may accelerate this process.

Relationship between the Corticospinal and Corticocerebellar Tracts and Their Role in Upper Extremity Motor Recovery in Stroke Patients.

The corticospinal tract (CST) and corticocerebellar tract (CCT) are both involved in the upper extremity (UE) function after stroke. Understanding the relationship between the tracts and their functions can contribute to developing patient-specific rehabilitative strategies. Seventy ischemic stroke patients who underwent diffusion tensor imaging (DTI) two weeks after the stroke onset and motor function assessments two weeks and three months after the stroke onset were included in this study. To obtain the CST and CCT integrity, the functional anisotropy (FA) values of both tracts were extracted from the DTI data. Linear regression was used to identify the relationship and predictive accuracy. The CST FA data had predictive values, but CCT FA did not. There were interaction effects between the CST and CCT FA values (p = 0.011). The CCT was significantly associated with high CST FA but not low CST FA. When the CST or CCT FA were applied to patients depending on the CST status, the stratified model showed higher predictive accuracy (R2 = 0.380) than that of the CST-only model (R2 = 0.320). In this study, the conditional role of CCT depending on CST status was identified in terms of UE recovery in stroke patients. This result could provide useful information about individualized rehabilitative strategies in stroke patients.

The Route of Motor Recovery in Stroke Patients Driven by Exoskeleton-Robot-Assisted Therapy: A Path-Analysis.

Background: Exoskeleton-robot-assisted therapy is known to positively affect the recovery of arm functions in stroke patients. However, there is a lack of evidence regarding which variables might favor a better outcome and how this can be modulated by other factors. Methods: In this within-subject study, we evaluated the efficacy of a robot-assisted rehabilitation system in the recovery of upper limb functions. We performed a path analysis using a structural equation modeling approach in a large sample of 102 stroke patients (age 63.6 ± 13.1 years; 61% men) in the post-acute phase. They underwent 7 weeks of bilateral arm training assisted by an exoskeleton robot combined with a conventional treatment (consisting of simple physical activity together with occupational therapy). The upper extremity section of the Fugl–Meyer (FM-UE) scale at admission was used as a predictor of outcome, whereas age, gender, side of the lesion, days from the event, pain scale, duration of treatment, and number of sessions as mediators. Results: FM-UE at admission was a direct predictor of outcome, as measured by the motricity index of the contralateral upper limb and trunk control test, without any other mediating factors. Age, gender, days from the event, side of lesion, and pain scales were independently associated with outcomes. Conclusions: To the best of our knowledge, this is the first study assessing the relationship between clinical variables and outcomes induced by robot-assisted rehabilitation with a path-analysis model. We define a new route for motor recovery of stroke patients driven by exoskeleton-robot-assisted therapy, highlighting the role of FM-UE at admission as a useful predictor of outcome, although other variables need to be considered in the time-course of disease.

Cerebrolysin Combined with Rehabilitation Enhances Motor Recovery and Prevents Neural Network Degeneration in Ischemic Stroke Patients with Severe Motor Deficits.

The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl–Meyer Assessment (p < 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.

Using Body Ownership to Modulate the Motor System in Stroke Patients

Recent findings suggest that body ownership can activate the motor system in the absence of movement execution. Here, we investigated whether such a process promotes motor recovery in stroke patients. A group of patients with left-hemisphere damage (N = 12) and chronic motor deficits completed an immersive virtual reality training (three sessions of 15 min each week for 11 weeks). Patients sat still and either experienced (first-person perspective) or did not experience (third-person perspective) illusory ownership over the body of a standing virtual avatar. After the training, in which the avatar walked around a virtual environment, only patients who experienced the illusion improved gait and balance. We argue that representing the virtual body as their own allowed patients to access motor functioning and promoted motor recovery. This procedure might be integrated with rehabilitative approaches centered on motor execution. These findings also have an impact on the knowledge of the motor system in general.

Proprioceptive Augmentation With Illusory Kinaesthetic Sensation in Stroke Patients Improves Movement Quality in an Active Upper Limb Reach-and-Point Task.

Stroke patients often have difficulty completing motor tasks even after substantive rehabilitation. Poor recovery of motor function can often be linked to stroke-induced damage to motor pathways. However, stroke damage in pathways that impact effective integration of sensory feedback with motor control may represent an unappreciated obstacle to smooth motor coordination. In this study we investigated the effects of augmenting movement proprioception during a reaching task in six stroke patients as a proof of concept. We used a wearable neurorobotic proprioceptive feedback system to induce illusory kinaesthetic sensation by vibrating participants' upper arm muscles over active limb movements. Participants were instructed to extend their elbow to reach-and-point to targets of differing sizes at various distances, while illusion-inducing vibration (90 Hz), sham vibration (25 Hz), or no vibration was applied to the distal tendons of either their biceps brachii or their triceps brachii. To assess the impact of augmented kinaesthetic feedback on motor function we compared the results of vibrating the biceps or triceps during arm extension in the affected arm of stroke patients and able-bodied participants. We quantified performance across conditions and participants by tracking limb/hand kinematics with motion capture, and through Fitts' law analysis of reaching target acquisition. Kinematic analyses revealed that injecting 90 Hz illusory kinaesthetic sensation into the actively contracting (agonist) triceps muscle during reaching increased movement smoothness, movement directness, and elbow extension. Conversely, injecting 90 Hz illusory kinaesthetic sensation into the antagonistic biceps during reaching negatively impacted those same parameters. The Fitts' law analyses reflected similar effects with a trend toward increased throughput with triceps vibration during reaching. Across all analyses, able-bodied participants were largely unresponsive to illusory vibrational augmentation. These findings provide evidence that vibration-induced movement illusions delivered to the primary agonist muscle involved in active movement may be integrated into rehabilitative approaches to help promote functional motor recovery in stroke patients.

Action Observation Therapy for Upper Limb Recovery in Patients with Stroke: A Randomized Controlled Pilot Study.

Due to the complexity of the interventions for upper limb recovery, at the moment there is a lack of evidence regarding innovative and effective rehabilitative interventions. Action Observation Training (AOT) constitutes a promising rehabilitative method to improve upper limb motor recovery in stroke patients. The aim of the present study was to evaluate the potential efficacy of AOT, both in upper limb recovery and in functional outcomes when compared to patients treated with task oriented training (TOT). Both treatments were added to traditional rehabilitative treatment. Thirty-two acute stroke patients at 15.6 days (±8.3) from onset, with moderate to severe upper limb impairment at baseline following their first-ever stroke, were enrolled and randomized into two groups: 16 in the experimental group (EG) and 16 in the control group (CG). The EG underwent 30 min sessions of AOT, and the CG underwent 30 min sessions of TOT. All participants received 20 sessions of treatment for four consecutive weeks (five days/week). The Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Box and Block Test (BBT), Functional Independence Measure (FIM) and Modified Ashworth Scale (MAS) were administered at baseline (T0) and at the end of treatment (T1). No statistical differences were found at T0 for inclusion criteria between the CG and EG, whereas both groups improved significantly at T1. After the treatment period, the rehabilitative gain was greater in the EG compared to the CG for FMA-UE and FIM (all p < 0.05). Our results suggest that AOT can contribute to increased motor recovery in subacute stroke patients with moderate to severe upper limb impairment in the early phase after stroke. The improvements presented in this article, together with the lack of adverse events, confirm that the use of AOT should be broadened out to larger pools of subacute stroke patients.

Development and Testing of a Virtual Reality Mirror Therapy System for the Sensorimotor Performance of Upper Extremity: A Pilot Randomized Controlled Trial

Mirror therapy (MT) has been proposed as an essential component of upper limb neurorehabilitation, using mirror illusion of the unaffected hand movement and superimposing it on the affected hand to improve neuroplasticity for improving motor recovery in stroke patients. In this paper, we developed a virtual reality mirror therapy (VRMT) system, and examined the performance of the proposed VRMT system. The VRMT system consists of a motion-tracking device, a VR goggle, and a VRMT software. Young, healthy participants, and stroke patients with mild-to-severe hemiparesis were recruited in this study, to validate the effectiveness of the proposed VRMT system. Experimental results based on the pinch-holding-up activity (PHUA) test revealed a significant effect on the precision pinch performance of young-healthy participants receiving VRMT, whereas traditional MT could not improve the precision pinch performance in young-healthy participants (Wilcoxon signed-rank test, Z = -2.693, p = 0.007). For patients having suffered a stroke and being treated with VRMT, significant beneficial effects examined by mixed effect model were found on the total score of FMA (p = 0.033) and hand part of FMA (p = 0.008). The findings in this study indicate that the VRMT system has a potentially positive effects on the sensorimotor performance of hands in healthy participants. In addition, add-on effect of VR to MT provides beneficial effects on motor function of the upper extremity in chronic stroke patients.

Assessing Stiffness, Joint Torque and ROM for Paretic and Non-Paretic Lower Limbs during the Subacute Phase of Stroke Using Lokomat Tools

The efficacy of Lokomat on motor recovery in stroke patients is well known. However, few studies have examined Lokomat tools to assess stiffness, joint torque and range of motion (ROM) during the subacute phase of stroke. The purpose of this retrospective observational study is to assess the changes of joint torque, ROM and stiffness that were estimated with Lokomat tools, namely L-FORCE (lower limb-force), L-ROM (lower limb-range of motion)and L-STIFF (lower limb-stiff), for paretic and non-paretic lower limbs in the subacute phase of stroke, assuming that the tools were able to measure these changes. The data come from 10 subjects in the subacute phase who had their first ever-stroke and followed a treatment that included Lokomat. The measurements came from basal assessments (T0) and one-month follow-up (T1). The measures were compared between paretic and non-paretic legs, and between T0 and T1. Significant differences in stiffness, joint torque and ROM were obtained between the paretic and non-paretic limbs at both T0 and T1. A non-significant trend was obtained for reduced stiffness and increased torque and ROM between T0 and T1 of the paretic limbs. The Lokomat tools were able to measure the changes between paretic and non-paretic legs and the small changes between T0 and T1 measurements.

Different Therapeutic Effects of Transcranial Direct Current Stimulation on Upper and Lower Limb Recovery of Stroke Patients with Motor Dysfunction: A Meta-Analysis.

Objective To explore the effects of transcranial direct current stimulation (tDCS) on the motor recovery of stroke patients and the effect differences between the upper limb and lower limb. Methods Randomized control trials published until January 2019 were searched from PubMed, Embase, ScienceDirect, and Cochrane Library databases. The standardized mean difference (SMD) with 95% confidence interval (CI) was estimated separately for upper and lower limb motor outcomes to understand the mean effect size. Results Twenty-nine studies with 664 subjects were included in this meta-analysis. The overall analyses of tDCS demonstrated significant effect size both for the upper limb (SMD = 0.26, P = 0.002) and the lower limb (SMD = 0.47, P = 0.002). Compared with acute and subacute stroke patients, chronic stroke patients obtained significant effects after tDCS (SMD = 0.25, P = 0.03) in upper limb function. Furthermore, both anode and cathode stimulations produced significant effect size for stroke patients after ≤10 sessions of tDCS (anode: SMD = 0.40, P = 0.001; cathode: SMD = 0.79, P < 0.0001) with >0.029 mA/cm2 of density (anode: SMD = 0.46, P = 0.002; cathode: SMD = 0.79, P < 0.0001). But for lower limb function, more prominent effects were found in subacute stroke patients (SMD = 0.56, P = 0.001) with bilateral tDCS (SMD = 0.59, p = 0.009). Conclusion tDCS is effective for the recovery of stroke patients with motor dysfunction. In addition, upper limb and lower limb functions obtain distinct effects from different therapeutic parameters of tDCS at different stages, respectively.

The Reorganization of Resting-State Brain Networks Associated With Motor Imagery Training in Chronic Stroke Patients.

A number of studies have suggested that motor imagery training (MIT) has a positive influence on the upper extremity motor recovery in stroke patients, but little is known about its neural basis. To investigate the cortical motor network plasticity after MIT, 34 chronic hemiplegic subjects with subcortical stroke were recruited and randomly allocated to either the conventional rehabilitation therapy (CRT) or the CRT + MIT. The patients were assessed with the upper limb section of Fugl-Meyer assessment Scale (FM-UL) and resting-state fMRI before and after the 4 weeks of treatment. Seed-based functional connectivity (FC) of the ipsilesional primary motor cortex (M1) and graph-theory based analysis were used to explore the relationships between the motor recovery and reorganization of motor networks. We found that the patients in the MIT group showed more improvement in the FM-UL scores compared with the CRT group. Both groups presented increased inter-hemispheric and decreased intra-hemispheric FC of the ipsilesional M1 after intervention. However, the MIT group showed increased FC of the ipsilesional M1 with the ipsilesional precentral and postcentral gyri, middle cingulate gyrus and supramarginal gyrus after intervention, while the CRT group showed decreased FC in these regions. In addition, the clustering coefficient was significantly increased in the MIT group but not in the CRT group, and the increment of clustering coefficient was significantly positively correlated with improvement of FM-UL scores. Therefore, MIT might contribute to the motor recovery in stroke patients through the following network reorganization, i.e., promoting the efficiency of regional neuronal communication and the reorganization of intrinsic FC of the ipsilesional M1 involving widely distributed motor network in both hemispheres.

Development of an EMG-Controlled Knee Exoskeleton to Assist Home Rehabilitation in a Game Context.

As a leading cause of loss of functional movement, stroke often makes it difficult for patients to walk. Interventions to aid motor recovery in stroke patients should be carried out as a matter of urgency. However, muscle activity in the knee is usually too weak to generate overt movements, which poses a challenge for early post-stroke rehabilitation training. Although electromyography (EMG)-controlled exoskeletons have the potential to solve this problem, most existing robotic devices in rehabilitation centers are expensive, technologically complex, and allow only low training intensity. To address these problems, we have developed an EMG-controlled knee exoskeleton for use at home to assist stroke patients in their rehabilitation. EMG signals of the subject are acquired by an easy-to-don EMG sensor and then processed by a Kalman filter to control the exoskeleton autonomously. A newly-designed game is introduced to improve rehabilitation by encouraging patients' involvement in the training process. Six healthy subjects took part in an initial test of this new training tool. The test showed that subjects could use their EMG signals to control the exoskeleton to assist them in playing the game. Subjects found the rehabilitation process interesting, and they improved their control performance through 20-block training, with game scores increasing from 41.3 ± 15.19 to 78.5 ± 25.2. The setup process was simplified compared to traditional studies and took only 72 s according to test on one healthy subject. The time lag of EMG signal processing, which is an important aspect for real-time control, was significantly reduced to about 64 ms by employing a Kalman filter, while the delay caused by the exoskeleton was about 110 ms. This easy-to-use rehabilitation tool has a greatly simplified training process and allows patients to undergo rehabilitation in a home environment without the need for a therapist to be present. It has the potential to improve the intensity of rehabilitation and the outcomes for stroke patients in the initial phase of rehabilitation.

The effect and optimal parameters of repetitive transcranial magnetic stimulation on motor recovery in stroke patients: a systematic review and meta-analysis of randomized controlled trials

Objective: The primary aim of this meta-analysis was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on limb movement recovery post-stroke and cortex excitability, to explore the optimal parameters of rTMS and suitable stroke population. Second, adverse events were also included. Data sources: The databases of PubMed, EBSCO, MEDLINE, the Cochrane Central Register of Controlled Trials, EBM Reviews-Cochrane Database, the Chinese National Knowledge Infrastructure, and the Chinese Science and Technology Journals Database were searched for randomized controlled trials exploring the effects of rTMS on limb motor function recovery post-stroke before December 2018. Review methods: The effect sizes of rTMS on limb motor recovery, the effect size of rTMS stimulation parameters, and different stroke population were summarized by calculating the standardized mean difference (SMD) and the 95% confidence interval using fixed/random effect models as appropriate. Results: For the motor function assessment, 42 eligible studies involving 1168 stroke patients were identified. The summary effect size indicated that rTMS had positive effects on limb motor recovery (SMD = 0.50, P < 0.00001) and activities of daily living (SMD = 0.82, P < 0.00001), and motor-evoked potentials of the stimulated hemisphere differed according to the stimulation frequency, that is, the high-frequency group (SMD = 0.57, P = 0.0006), except the low-frequency group (SMD = –0.27, P = 0.05). No significant differences were observed among the stimulation parameter subgroups except for the sessions subgroup (P = 0.02). Only 10 included articles reported transient mild discomfort after rTMS. Conclusions: rTMS promoted the recovery of limb motor function and changed the cortex excitability. rTMS may be better for early and pure subcortical stroke patients. Regarding different stimulation parameters, the number of stimulation sessions has an impact on the effect of rTMS.

Long-term, non-invasive brain stimulation for locked-in syndrome

Background & significance: Locked-in syndrome is a very serious condition with desperate quality of life due to profound paralysis, and there is no effective treatment other than rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) seems to be benefit in motor recovery of stroke patients. We explored the benefit and feasibility of rTMS in locked-in syndrome.