Upper-extremity Motor Impairment Research Articles

Efficacy and Safety of High-Dose TBS on Post-Stroke Upper Extremity Motor Impairment: A Randomized Controlled Trial.

Upper extremity (UE) motor function impairment is a major poststroke complication whose recovery remains one of the most challenging tasks in neurological rehabilitation. This study examined the efficacy and safety of the personalized neuroimaging-guided high-dose theta-burst stimulation (TBS) for poststroke UE motor function recovery. Patients after stroke with UE motor impairment from a China rehabilitation center were randomly assigned to receive high-dose intermittent TBS (iTBS) to ipsilesional UE sensorimotor network, continuous TBS (cTBS) to contralesional UE sensorimotor network, or sham stimulation, along with conventional therapy for 3 weeks. The primary outcome was the score changes on the Fugl-Meyer assessment-UE from baseline to 1 and 3 weeks. The secondary outcomes included the response rate on Fugl-Meyer assessment-UE scores posttreatment (≥9-point improvement) and score changes in multidimensional scales measuring UE, lower extremity, and activities and participation. From June 2021 to June 2022, 45 participants were randomized and 43 were analyzed. The iTBS and continuous TBS groups showed significantly greater improvement in Fugl-Meyer assessment-UE (mean improvement, iTBS: 10.73 points; continuous TBS: 10.79 points) than the sham group (2.43 points) and exhibited significantly greater response rates on Fugl-Meyer assessment-UE (iTBS, 60.0%; continuous TBS, 64.3%) than the sham group (0.0%). The active groups consistently exhibited superior improvement on the other 2 UE assessments at week 3. However, only the iTBS group showed greater efficacy on 1 lower extremity assessment than the sham group at week 3. Both active groups showed significant improvements in activities and participation assessments. The study provides evidence for the efficacy and safety of high-dose TBS in facilitating poststroke UE rehabilitation. URL: www.chictr.org.cn; Unique identifier: ChiCTR2100047340.

Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study.

Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. https://clinicaltrials.gov/, identifier NCT06270238.

Vagus Nerve Stimulation Paired With Upper Extremity Rehabilitation for Chronic Ischemic Stroke: Contribution of Dosage Parameters

Background Vagus nerve stimulation (VNS) combined with rehabilitation is a Food and Drug Administration approved intervention for moderate to severe upper extremity deficits in chronic ischemic stroke patients. Previous studies demonstrated that VNS improves upper extremity motor impairments, using the Fugl Meyer Assessment of Upper Extremity (FMA-UE); however, delineating where these improvements occur, and the role of VNS dosage parameters were not reported. Objective This study explored the relationship between dosing (time over which task repetitions were executed and number of VNS stimulations) and changes within proximal and distal components of the FMA-UE. Methods Participants underwent VNS implantation, with 1 group receiving VNS paired with rehabilitation (Active VNS) and the other group receiving rehabilitation with sham stimulation (Controls). Both groups received 6 weeks of in-clinic therapy followed by a 90-day at-home, self-rehabilitation program. Participants who completed at least 12 of 18 in-clinic sessions were included in the analyses (n = l06). Pearson correlations and analysis of covariance were used to investigate the relationship between dosing and FMA-UE outcome change along with the effect of covariates including baseline severity, time since stroke, age, and paretic side. Results Compared to Controls, active VNS favorably influenced distal function with sustained improvement after the home program. Significant improvements were observed in only distal components (FMdist) at both post day-1 (1.80 points, 95% Cl [0.85, 2.73], P < .001) and post-day 90 (1.62 points, 95% CI [0.45, 2.80], P < .007). Conclusions VNS paired with rehabilitation resulted in significant improvements in wrist and hand impairment compared to Controls, despite similar in-clinic dosing across both groups. NCT03131960

Examining Sex Differences in Relationships Between Subjective and Objective Measures of Upper Extremity Motor Impairment in a Sample of Stroke Survivors.

Rehabilitation professionals use subjective and objective outcome measures to assess stroke-related impact and impairment. Understanding if subjective and objective findings correlate among stroke survivors, especially if these associations differ between females and males, can inform care decisions. A retrospective cross-sectional design was used, with data selected from subacute to chronic stroke survivors on age, time since stroke, the hand domain from the Stroke Impact Scale version 3.0 (SIS-H), and the Fugl-Meyer Upper Extremity (FMUE) Assessment. Group differences were assessed for all outcomes based on sex and time poststroke. Separate correlations for females and males were performed between the subjective (SIS-H) and objective measures (FMUE) of upper limb function and impairment. Data from 148 participants (44 females) were included in this study. SIS-H was significantly correlated with FMUE in both females and males ( P s ≤0.001). No significant differences were found between the groups' mean SIS-H or FMUE scores based on sex or time poststroke. Subjective and objective measures of physical functioning were correlated in both females and males. Although we found no sex differences in our primary outcomes, the sample size of females was disproportionately lower than the males. This is consistent with an ongoing problem in the stroke recovery research field, where females are often underrepresented and understudied, and where females who experience higher levels of impairment are less likely to participate in research.

The effects of trunk repositioning errors on trunk and extremity functions in stroke

ABSTRACT Aim The aim of this study was to analyze the TRE in three directions including forward flexion, lateral flexion to the hemiparetic side, and rotation to the hemiparetic side in patients with stroke and to compare the errors with age- and sex-matched healthy subjects. In addition, it was investigated which functional outcomes were explanatory for TRE in patients with stroke. Methods Forty-one patients with subacute/chronic stroke (age 59 ± 14.5 years) and 41 healthy subjects (age 57 ± 12.8 years) were included in the study. Demographic and clinical data were collected. TREs were measured using an inclinometer. The Trunk Impairment Scale (TIS), Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), Timed Up and Go Test, and 10-m walk test (10MWT) were also used to assess trunk control, motor impairment, upper extremity function, and lower extremity function, respectively, in patients with stroke. Results TRE scores in three directions were higher in patients with stroke than in healthy subjects (p < 0.001). TREs in three directions were significantly strongly correlated with all functional outcomes (ρ > 0.60, r < 0.001). Multiple regression analysis determined 10MWT, WMFT-Performance, TIS, and FMA-Upper Extremity as explanatory factors for TRE. Conclusion The model presented in this study could help clinicians and researchers to predict the TRE in patients with stroke. Gait speed, upper extremity motor ability, upper extremity motor impairment, and trunk control should be considered for TRE after a stroke.

The stratified effects of repetitive transcranial magnetic stimulation in upper limb motor impairment recovery after stroke: a meta-analysis.

The recovery of upper extremity motor impairment after stroke remains a challenging task. The clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS), which is believed to aid in the recovery process, is still uncertain. A systematic search was conducted in Medline (Ovid), Cochrane and Embase electronic databases from March 28, 2014, to March 28, 2023. The inclusion criteria consisted of randomized controlled trials that assessed the effects of rTMS on the recovery of upper limb motor impairment among stroke patients. Various measurements, including the Fugl Meyer Assessment Upper Extremity Scale (FMA-UE), Brunnstrom recovery stage, Action Research Arm Test (ARAT), and Barthel index, were evaluated both before and after the intervention. Nineteen articles with 865 patients were included. When considering only the rTMS parameters, both inhibitory and excitatory rTMS improved FMA-UE (MD = 1.87, 95% CI = [0.88]-[2.86], p < 0.001) and Barthel index (MD = 9.73, 95% CI = [4.57]-[14.89], p < 0.001). When considering only the severity of upper limb hemiplegia, both less severe (MD = 1.56, 95% CI = [0.64]-[2.49], p < 0.001) and severe (MD = 2.05, 95% CI = [1.09]-[3.00], p < 0.001) hemiplegia benefited from rTMS based on FMA-UE. However, when considering the rTMS parameters, severity of hemiplegia and stroke stages simultaneously, inhibitory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 4.55, 95% CI = [2.49]-[6.60], p < 0.001), but not in the chronic phase based on FMA-UE. For severe hemiplegia, inhibitory rTMS was not significantly effective in the acute and subacute phases, but significantly effective in the chronic phase (MD = 2.10, 95% CI = [0.75]-[3.45], p = 0.002) based on FMA-UE. Excitatory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 1.93, 95% CI = [0.58]-[3.28], p = 0.005) based on FMA-UE. The improvements in Brunnstrom recovery stage and ARAT need further research. The effectiveness of rTMS depends on its parameters, severity of hemiplegia, and stroke stages. It is important to consider all these factors together, as any single grouping method is incomplete.

Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials.

In 2021, the U.S. Food and Drug Administration (FDA) approved paired vagus nerve stimulation (VNS) for patients with moderate-to-severe upper extremity motor impairments following chronic ischemic stroke. Previous meta-analyses have shown that VNS may impact stroke rehabilitation, but each has some limitations. PubMed, Ovid, Cochrane Library, ScienceDirect, Web of Science and WHO ICTRP databases were searched until July 14, 2022 for randomized controlled trials (RCTs). We defined primary outcomes as Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT). Subgroup analyses included types of VNS, time since onset and long-term effects. Secondary outcomes included adverse events of VNS. Eight RCTs involving 266 patients were analyzed, of which five used direct VNS and three transcutaneous auricular VNS. The results revealed that VNS enhanced upper extremity function via FMA-UE (SMD = 0.73; 95% CI: 0.48 to 0.99; P < 0.00001) and WMFT (SMD = 0.82; 95% CI:0.52 to 1.13; P < 0.00001) in comparison to the control group, but showed no significant change on long-term effects of FMA-UE (SMD = 0.69; 95% CI: - 0.06 to 1.44; P = 0.07). There was no difference in adverse events between the VNS and control groups (RR = 1.16; 95% CI: 0.46 to 2.92; P = 0.74). For stroke victims with upper limb disabilities, VNS paired with rehabilitation was significantly safe and effective. More high-quality multicentric RCTs are needed to validate this conclusion.

Interactive scalp acupuncture for hemiplegic upper extremity motor dysfunction in patients with ischemic stroke: a randomized controlled trial

To compare the curative effect between interactive scalp acupuncture and traditional scalp acupuncture on hemiplegic upper extremity motor dysfunction in the patients with ischemic stroke. Seventy cases of hemiplegic upper extremity motor dysfunction of ischemic stroke were randomly divided into an interactive scalp acupuncture group (35 cases, 1 case breaked off) and a traditional scalp acupuncture group (35 cases, 1 case dropped off). The patients of the two groups received the secondary prevention medication and routine rehabilitation therapy. Besides, in the interactive scalp acupuncture group, the upper extremity occupational therapy was operated during the needle retaining of scalp acupuncture; and in the traditional scalp acupuncture group, the upper extremity occupational therapy was delivered after the completion of scalp acupuncture. The same points were selected in the two groups such as Fuxiang head area, Fuxiang upper-limb-shoulder point, Fuxiang upper-limb-elbow point and Fuxiang upper-limb-wrist point. The needles were inserted perpendicularly by flying-needle technique and manipulated by triple technique of gentle twisting, heavy pressure and vibrating. The needles were retained for 30 min. Based on the degree of the upper extremity motor impairment, the regimen of the upper extremity occupational therapy was formulated individually and one treatment took 30 min. In the two groups, the therapies were delivered once daily, 5 times a week, lasting 4 weeks. Before and after treatment, the scores of Fugl-Meyer assessment of upper extremity (FMA-UE), Wolf motor function test (WMFT), the modified Barthel index (MBI) and the modified Ashworth scale (MAS) grade in the two groups were observed before and after treatment. After treatment, the scores of FMA-UE, WMFT and MBI were higher than those before treatment (P<0.01), and MAS grade was improved (P<0.05) in the two groups. The scores of FMA-UE, WMFT and MBI in the interactive scalp acupuncture group were higher than those in the traditional scalp acupuncture group (P<0.01, P<0.05), and there was no statistical significance in the difference of MAS grade between the two groups (P>0.05). The interactive scalp acupuncture can effectively improve the motor function of the hemiplegic upper extremities and the activities of daily living in the patients with ischemic stroke and its efficacy is better than traditional scalp acupuncture. But these two types of scalp acupuncture obtain the similar effect on spasticity.

Lifetime and Acute Stress Predict Functional Outcomes Following Stroke: Findings From the Longitudinal STRONG Study.

Stroke is a sudden-onset, uncontrollable event; stroke-related stress may impede rehabilitation and recovery. Lifetime stress may sensitize patients to experiencing greater stroke-related stress and indirectly affect outcomes. We examine lifetime stress as predictor of poststroke acute stress and examine lifetime and acute stress as predictors of 3- and 12-month functional status. We also compare acute stress and baseline National Institutes of Health Stroke Scale as predictors of poststroke functional status. Between 2016 and 2020 the STRONG Study (Stroke, Stress, Rehabilitation, and Genetics) enrolled adults with new radiologically confirmed stroke 2 to 10 days poststroke onset at 28 acute care US hospitals. Participants were interviewed 3 times: acute admission (acute stress; Acute Stress Disorder Interview), 3 months (Fugl-Meyer Upper Extremity motor impairment [Fugl-Meyer Upper Arm Assessment; N=431], modified Rankin Scale [3 months; N=542], Stroke Impact Scale-Activities of Daily Living [3 months; N=511], Lifetime Stress Exposure Inventory), and 12 months (modified Rankin Scale, N=533; Stroke Impact Scale 3.0 Activities of Daily Living; N=485; Telephone Montreal Cognitive Assessment; N=484) poststroke. Structural equation models examined whether acute stress predicted 3- and 12-month functional outcomes, and mediated an association between lifetime stress and outcomes controlling for demographics and initial National Institutes of Health Stroke Scale. Standardized betas are reported. Sample (N=763) was 19 to 95 years old (mean=63; SD=14.9); 448 (58.7%) were male. Acute stress scores ranged from 0 to 14 (mean, 3.52 [95% CI, 3.31-3.73]). Controlling for age, gender, baseline National Institutes of Health Stroke Scale, and race and ethnicity, higher lifetime stress predicted higher acute stress (β=0.18, P<0.001), which predicted lower 3-month Fugl-Meyer Upper Arm Assessment scores (β=-0.19, P<0.001), lower Stroke Impact Scale 3.0 Activities of Daily Living scores at 3 months (β=-0.21, P<0.001) and 12 months (β=-0.21, P<0.001), higher modified Rankin Scale scores at 3 months (β=0.23, P<0.001) and 12 months (β=0.22, P<0.001), and lower 12-month Telephone Montreal Cognitive Assessment scores (β=-0.20, P<0.001). Acute stress predicted 12-month tMoCA (χ2[1]=5.29, P=0.022) more strongly, 3-month and 12-month modified Rankin Scale and SIS scores as strongly (all Ps>0.18), but Fugl-Meyer scores (χ2[1]=7.01, P=0.008) less strongly than baseline National Institutes of Health Stroke Scale. Lifetime stress/trauma is associated with more poststroke acute stress, which is associated with greater motor and cognitive impairment and disability 3 and 12 months poststroke. Poststroke interventions for acute stress may help mitigate stroke-related disability.

Sensitivity to Change and Responsiveness of the Upper Extremity Fugl-Meyer Assessment in Individuals With Moderate to Severe Acute Stroke.

The Fugl-Meyer Assessment-Upper Extremity (FMA-UE) is a widely used outcome measure for quantifying motor impairment in stroke recovery. Meaningful change (responsiveness) in the acute to subacute phase of stroke recovery has not been determined. Determine responsiveness and sensitivity to change of the FMA-UE from 1-week to 6-weeks (subacute) after stroke in individuals with moderate to severe arm impairment who received standard clinical care. A total of 51 participants with resulting moderate and severe UE hemiparesis after stroke had FMA-UE assessment at baseline (within 2 weeks of stroke) and 6-weeks later. Sensitivity to change was assessed using Glass's delta, standardized response means (SRM), standard error of measure (SEM), and minimal detectable change (MDC). Responsiveness was assessed with the minimal clinically important difference (MCID), estimated using receiver operating characteristic curve analysis with patient-reported global rating of change scales (GROC) and a provider-reported modified Rankin Scale (mRS) as anchors. The MCID estimates were 13, 12, and 9 anchored to the GROC Arm Weakness, GROC Recovery, and mRS. Glass's delta and the SRM revealed large effect sizes, indicating high sensitivity to change, (∆ = 1.24, 95% CI [0.64, 1.82], SRM = 1.10). Results for the SEM and MDC were 2.46 and 6.82, respectively. The estimated MCID for the FMA-UE for individuals with moderate to severe motor impairment from 1 to 6-weeks after stroke is 13. These estimates will provide clinical context for FMA-UE change scores by helping to identify the change in upper-extremity motor impairment that is both beyond measurement error and clinically meaningful.

Do kinematic measures, added to clinical measures, better predict upper extremity motor impairments at three months post-stroke?

ObjectivePredicting post-stroke recovery through prediction models is crucial for choosing appropriate treatment options. However, the existing models predominantly incorporate clinical measures although measurement of movement quality using kinematic measures is essential for distinguishing various types of recovery. Thus, this study aimed at determining if, by considering varied aspects of recovery, adding kinematic measurements over clinical measures would better predict upper extremity (UE) motor impairments at three months post-stroke. Materials and methodsEighty-nine stroke survivors (58.9 ± 11.8 years) were assessed for clinical predictors between 4 and 7 days, kinematic predictors within 1 month, and the impairment outcome of the Fugl Meyer Assessment of the UE (FM-UE) at three months post-stroke. Significant predictors (p<0.05) with a variation inflation factor (VIF) <10 were selected for model development. After performing further step-wise selection, three models incorporating clinical outcomes, kinematic measurements, and a combination of these two, respectively, were formulated. ResultsThe clinical model (R2 = 0.70) included shoulder abduction finger extension (SAFE) scores, the National Institutes of Health Stroke Scale (NIHSS), and the Montreal Cognitive Assessment (MoCA). The kinematic model (R2 = 0.34) included total displacement, total time, and reaction time. The combined model (R2 = 0.72) comprised of SAFE score and shoulder flexion. All the models had a minimal mean squared error on cross validation, which indicated a good validity. ConclusionThe performance of clinical and combined prediction models for predicting three-month post-stroke UE motor recovery was nearly similar. However, in order to detect minimal changes over time and to understand all aspects of motor recovery, there is a need to add instrument-based kinematic measures.

Post-Stroke Rehabilitation of Distal Upper Limb with New Perspective Technologies: Virtual Reality and Repetitive Transcranial Magnetic Stimulation-A Mini Review.

Upper extremity motor impairment is the most common sequelae in patients with stroke. Moreover, its continual nature limits the optimal functioning of patients in the activities of daily living. Because of the intrinsic limitations in the conventional form of rehabilitation, the rehabilitation applications have been expanded to technology-driven solutions, such as Virtual Reality and Repetitive Transcranial Magnetic Stimulation (rTMS). The motor relearning processes are influenced by variables, such as task specificity, motivation, and feedback provision, and a VR environment in the form of interactive games could provide novel and motivating customized training solutions for better post-stroke upper limb motor improvement. rTMS being a precise non-invasive brain stimulation method with good control of stimulation parameters, has the potential to facilitate neuroplasticity and hence a good recovery. Although several studies have discussed these forms of approaches and their underlying mechanisms, only a few of them have specifically summarized the synergistic applications of these paradigms. To bridge the gaps, this mini review presents recent research and focuses precisely on the applications of VR and rTMS in distal upper limb rehabilitation. It is anticipated that this article will provide a better representation of the role of VR and rTMS in distal joint upper limb rehabilitation in patients with stroke.

Spinal cord H-reflex post-activation depression is linked with hand motor control in adults with cerebral palsy

ObjectiveCerebral palsy (CP) is associated with upper extremity motor impairments that are largely assumed to arise from alterations in the supraspinal networks. The objective of this study was to determine if post-activation depression of the spinal H-reflexes is altered in adults with CP and connected with altered upper extremity function. MethodsThe post-activation depression of the flexor carpi radialis (FCR) H-reflex of adults with CP and healthy adults (HA) controls were assessed by 1) a 1 Hz continuous single-pulse stimulus train and 2) 0.11 Hz / 1 Hz paired-pulse stimuli. Secondarily, we measured the maximum key grip force and the box and blocks assessment of manual dexterity. ResultsOur results revealed that adults with CP had reduced post-activation depression of the FCR H-reflex during the stimulus train and the paired pulse protocol. A greater reduction in H-reflex post-activation depression was connected to lower manual dexterity and weaker grip forces. ConclusionsOur results indicate that the post-activation depression of the upper extremity spinal H-reflex pathways is altered in adults with CP and possibly linked with their uncharacteristic upper extremity motor performance. Alterations in the spinal networks may also play a significant role in the altered motor control of adults with CP. SignificanceOur results identify spinal H-reflex modulation as a possible locus for hand motor control in CP.

Novel Platform for Quantitative Assessment of Functional Object Interactions After Stroke.

Many persons with stroke exhibit upper extremity motor impairments. These impairments often lead to dysfunction and affect performance in activities of daily living, where successful manipulation of objects is essential. Hence, understanding how upper extremity motor deficits manifest in functional interactions with objects is critical for rehabilitation. However, quantifying skill in these tasks has been a challenge. Traditional rehabilitation assessments require highly trained clinicians, are time-consuming, and yield subjective scores. This paper introduces a custom-designed device, the "MAGIC Table", that can record real-time kinematics of persons with stroke during interaction with objects, specifically a 'cup of coffee'. The task and its quantitative assessments were derived from previous basic-science studies. Six participants after stroke and six able-bodied participants moved a 3D-printed cup with a rolling ball inside, representing sloshing coffee, with 3 levels of difficulty. Movements were captured via a high-resolution camera above the table. Conventional kinematic metrics (movement time and smoothness) and novel kinematic metrics accounting for object interaction (risk and predictability) evaluated performance. Expectedly, persons with stroke moved more slowly and less smoothly than able-bodied participants, in both simple reaches and during transport of the cup-and-ball system. However, the more sensitive metric was mutual information, which captured the predictability of interactions, essential in cup transport as shown in previous theoretical research. Predictability sensitively measured differences in performance with increasing levels of difficulty. It also showed the best intraclass consistency, promising sensitive differentiation between different levels of impairment. This study highlights the feasibility of this new device and indicates that examining dynamic object interaction may provide valuable insights into upper extremity function after stroke useful for assessment and rehabilitation.

Resting-state functional connectivity for determining outcomes in upper extremity function after stroke: A functional near-infrared spectroscopy study

Functional near-infrared spectroscopy (fNIRS) is a non-invasive and promising tool to map the brain functional networks in stroke recovery. Our study mainly aimed to use fNIRS to detect the different patterns of resting-state functional connectivity (RSFC) in subacute stroke patients with different degrees of upper extremity motor impairment defined by Fugl-Meyer motor assessment of upper extremity (FMA-UE). The second aim was to investigate the association between FMA-UE scores and fNIRS-RSFC among different regions of interest (ROIs) in stroke patients. Forty-nine subacute (2 weeks-6 months) stroke patients with subcortical lesions were enrolled and were classified into three groups based on FMA-UE scores: mild impairment (n = 17), moderate impairment (n = 13), and severe impairment (n = 19). All patients received FMA-UE assessment and 10-min resting-state fNIRS monitoring. The fNIRS signals were recorded over seven ROIs: bilateral dorsolateral prefrontal cortex (DLPFC), middle prefrontal cortex (MPFC), bilateral primary motor cortex (M1), and bilateral primary somatosensory cortex (S1). Functional connectivity (FC) was calculated by correlation coefficients between each channel and each ROI pair. To reveal the comprehensive differences in FC among three groups, we compared FC on the group level and ROI level. In addition, to determine the associations between FMA-UE scores and RSFC among different ROIs, Spearman's correlation analyses were performed with a significance threshold of p < 0.05. For easy comparison, we defined the left hemisphere as the ipsilesional hemisphere and flipped the lesional right hemisphere in MATLAB R2013b. For the group-level comparison, the one-way ANOVA and post-hoc t-tests (mild vs. moderate; mild vs. severe; moderate vs. severe) showed that there was a significant difference among three groups (F = 3.42, p = 0.04) and the group-averaged FC in the mild group (0.64 ± 0.14) was significantly higher than that in the severe group (0.53 ± 0.14, p = 0.013). However, there were no significant differences between the mild and moderate group (MD ± SE = 0.05 ± 0.05, p = 0.35) and between the moderate and severe group (MD ± SE = 0.07 ± 0.05, p = 0.16). For the ROI-level comparison, the severe group had significantly lower FC of ipsilesional DLPFC-ipsilesional M1 [p = 0.015, false discovery rate (FDR)-corrected] and ipsilesional DLPFC-contralesional M1 (p = 0.035, FDR-corrected) than those in the mild group. Moreover, the result of Spearman's correlation analyses showed that there were significant correlations between FMA-UE scores and FC of the ipsilesional DLPFC-ipsilesional M1 (r = 0.430, p = 0.002), ipsilesional DLPFC-contralesional M1 (r = 0.388, p = 0.006), ipsilesional DLPFC-MPFC (r = 0.365, p = 0.01), and ipsilesional DLPFC-contralesional DLPFC (r = 0.330, p = 0.021). Our findings indicate that different degrees of post-stroke upper extremity impairment reflect different RSFC patterns, mainly in the connection between DLPFC and bilateral M1. The association between FMA-UE scores and the FC of ipsilesional DLPFC-associated ROIs suggests that the ipsilesional DLPFC may play an important role in motor-related plasticity. These findings can help us better understand the neurophysiological mechanisms of upper extremity motor impairment and recovery in subacute stroke patients from different perspectives. Furthermore, it sheds light on the ipsilesional DLPFC-bilateral M1 as a possible neuromodulation target.

Network Meta-Analysis of Non-Conventional Therapies for Improving Upper Limb Motor Impairment Poststroke.

Network meta-analysis is a method that can estimate relative efficacy between treatments that may not have been compared directly within the literature. The purpose of this study is to present a network meta-analysis of non-conventional interventions to improve upper extremity motor impairment after stroke. A literature search was conducted in 5 databases from their inception until April 1, 2021. Terms were used to narrow down articles related to stroke, the upper extremity, and interventional therapies. Randomized controlled trials written in English were eligible if; 50% poststroke patients; ≥18 years old; applied an intervention for the upper extremity, and/or used the Fugl-Meyer upper extremity scale as an outcome measure; the intervention had ≥3 randomized controlled trials with comparisons against a conventional care group; conventional care groups were dose matched for therapy time. A Bayesian network meta-analysis approach was taken to estimate mean difference (MD) and 95% CI. One hundred seventy-six randomized controlled trials containing 6781 participants examining 20 non-conventional interventions were identified for inclusion within the final model. Eight of the identified interventions proved significantly better than conventional care, with modified constraint induced movement therapy (MD, 6.7 [95% CI, 4.3-8.9]), high frequency repetitive transcranial magnetic stimulation (MD, 5.4 [95% CI, 1.9-8.9]), mental imagery (MD, 5.4 [95% CI, 1.8-8.9]), bilateral arm training (MD, 5.2 [95% CI, 2.2-8.1]), and intermittent theta-burst stimulation (MD, 5.1 [95% CI, 0.62-9.5]) occupying the top 5 spots according to the surface under the cumulative ranking curve. Overall, it would seem that modified constraint induced movement therapy has the greatest probability of being the most effective intervention, with high-frequency repetitive transcranial magnetic stimulation, mental imagery, and bilateral arm training all having similar probabilities of occupying the next spot in the rankings. We think this analysis can provide a guide for where future resources and clinical trials should be directed, and where a clinician may begin when considering alternative therapeutic interventions.

Barriers to Enrollment in Post-Stroke Brain Stimulation in a Racially and Ethnically Diverse Population

Background and Purpose Brain stimulation is an adjuvant strategy to promote rehabilitation after stroke. Here, we evaluated the influence of inclusion/exclusion criteria on enrollment in a transcranial direct current stimulation (tDCS) trial in the context of a racially/ethnically diverse acute stroke service at University of Texas Southwestern (UTSW). Methods 3124 (59.7 ± 14.5 years) racially/ethnically diverse (38.4% non-Hispanic white, (W), Hispanic (H) 22%, African American (AA) 33.5%, Asian (A) 2.3%) patients were screened in the acute stroke service at UTSW. Demographics, stroke characteristics, and reasons for exclusion were recorded prospectively. Results 2327 (74.5%) patients had a verified stroke. Only 44 of them (1.9%) were eligible. Causes for exclusion included in order of importance: (1) magnitude of upper extremity (UE) motor impairment, (2) prior strokes (s), (3) hemorrhagic stroke, (4) psychiatric condition or inability to follow instructions, and (5) old age, of these (2) and (4) were more common in AA patients but not in other minorities. 31 of the 44 eligible individuals were enrolled (W 1.68%, H 1.37%, AA .77%, A 3.774%). 90.5% of verified stroke patients did not exhibit contraindications for stimulation. Conclusions 3 main conclusions emerged: (a) The main limitations for inclusion in brain stimulation trials of motor recovery were magnitude of UE motor impairments and stroke lesion characteristics, (b) most stroke patients could be stimulated with tDCS without safety concerns and (c) carefully tailored inclusion criteria could increase diversity in enrollment. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT01007136.

BCI-FES With Multimodal Feedback for Motor Recovery Poststroke.

An increasing number of research teams are investigating the efficacy of brain-computer interface (BCI)-mediated interventions for promoting motor recovery following stroke. A growing body of evidence suggests that of the various BCI designs, most effective are those that deliver functional electrical stimulation (FES) of upper extremity (UE) muscles contingent on movement intent. More specifically, BCI-FES interventions utilize algorithms that isolate motor signals—user-generated intent-to-move neural activity recorded from cerebral cortical motor areas—to drive electrical stimulation of individual muscles or muscle synergies. BCI-FES interventions aim to recover sensorimotor function of an impaired extremity by facilitating and/or inducing long-term motor learning-related neuroplastic changes in appropriate control circuitry. We developed a non-invasive, electroencephalogram (EEG)-based BCI-FES system that delivers closed-loop neural activity-triggered electrical stimulation of targeted distal muscles while providing the user with multimodal sensory feedback. This BCI-FES system consists of three components: (1) EEG acquisition and signal processing to extract real-time volitional and task-dependent neural command signals from cerebral cortical motor areas, (2) FES of muscles of the impaired hand contingent on the motor cortical neural command signals, and (3) multimodal sensory feedback associated with performance of the behavioral task, including visual information, linked activation of somatosensory afferents through intact sensorimotor circuits, and electro-tactile stimulation of the tongue. In this report, we describe device parameters and intervention protocols of our BCI-FES system which, combined with standard physical rehabilitation approaches, has proven efficacious in treating UE motor impairment in stroke survivors, regardless of level of impairment and chronicity.

PrimSeq: A deep learning-based pipeline to quantitate rehabilitation training.

Stroke rehabilitation seeks to accelerate motor recovery by training functional activities, but may have minimal impact because of insufficient training doses. In animals, training hundreds of functional motions in the first weeks after stroke can substantially boost upper extremity recovery. The optimal quantity of functional motions to boost recovery in humans is currently unknown, however, because no practical tools exist to measure them during rehabilitation training. Here, we present PrimSeq, a pipeline to classify and count functional motions trained in stroke rehabilitation. Our approach integrates wearable sensors to capture upper-body motion, a deep learning model to predict motion sequences, and an algorithm to tally motions. The trained model accurately decomposes rehabilitation activities into elemental functional motions, outperforming competitive machine learning methods. PrimSeq furthermore quantifies these motions at a fraction of the time and labor costs of human experts. We demonstrate the capabilities of PrimSeq in previously unseen stroke patients with a range of upper extremity motor impairment. We expect that our methodological advances will support the rigorous measurement required for quantitative dosing trials in stroke rehabilitation.

Baseline Predictors of Response to Repetitive Task Practice in Chronic Stroke

Background Repetitive task practice reduces mean upper extremity motor impairment in populations of patients with chronic stroke, but individual response is highly variable. A method to predict meaningful reduction in impairment in response to training based on biomarkers and other data collected prior to an intervention is needed to establish realistic rehabilitation goals and to effectively allocate resources. Objectives To identify prognostic factors and better understand the biological substrate for reductions in arm impairment in response to repetitive task practice among patients with chronic (≥6 months) post-stroke hemiparesis. Methods The intervention is a form of repetitive task practice using a combination of robot-assisted therapy and functional arm use in real-world tasks. Baseline measures include the Fugl-Meyer Assessment, Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, MRI, transcranial magnetic stimulation, kinematics, accelerometry, and genomic testing. Results Mean increase in FM-UE was 4.6 ± 1.0 SE, median 2.5. Approximately one-third of participants had a clinically meaningful response to the intervention, defined as an increase in FM ≥ 5. The selected logistic regression model had a receiver operating curve with AUC = .988 (Std Error = .011, 95% Wald confidence limits: .967–1) showed little evidence of overfitting. Six variables that predicted response represented impairment, functional, and genomic measures. Conclusion A simple weighted sum of 6 baseline factors can accurately predict clinically meaningful impairment reduction after outpatient intensive practice intervention in chronic stroke. Reduction of impairment may be a critical first step to functional improvement. Further validation and generalization of this model will increase its utility in clinical decision-making.