Heteronymous feedback from quadriceps onto soleus in stroke survivors.

Background: Recent findings suggest increased excitatory heteronymous feedback from quadriceps onto soleus may contribute to abnormal coactivation of knee and ankle extensors after stroke. However, there is lack of consensus on whether persons post-stroke exhibit altered heteronymous reflexes and, when present, the origin of increased excitation (i.e. increased excitation alone and/or decreased inhibition). This study examined heteronymous excitation and inhibition from quadriceps onto soleus in paretic, nonparetic, and age-matched control limbs to determine whether increased excitation was due to excitatory and/or reduced inhibitory reflex circuits. A secondary purpose was to examine whether heteronymous reflex magnitudes were related to clinical measures of lower limb recovery, walking-speed, and dynamic balance. Methods: Heteronymous excitation and inhibition from quadriceps onto soleus were examined in fourteen persons post-stroke and fourteen age-matched unimpaired participants. Heteronymous feedback was elicited by femoral nerve and quadriceps muscle stimulation in separate trials while participants tonically activated soleus at 20% max. Fugl-Myer assessment of lower extremity, 10-meter walk test, and Mini-BESTest were assessed in stroke survivors. Results: Heteronymous excitation and inhibition onsets, durations, and magnitudes were not different between paretic, nonparetic or age-matched unimpaired limbs. Quadriceps stimulation elicited excitation that was half the magnitude of femoral nerve stimulation. Femoral nerve elicited paretic limb heteronymous excitation was positively correlated with walking speed but did not reach significance because only a subset of paretic limbs exhibited excitation (n = 8, Spearman r = 0.69, P = 0.058). Conclusions: Heteronymous feedback from quadriceps onto soleus assessed in a seated posture was not impaired in persons post-stroke. Despite being unable to identify whether reduced inhibition contributes to abnormal excitation reported in prior studies, our results indicate quadriceps stimulation may allow a better estimate of heteronymous inhibition in those that exhibit exaggerated excitation. Heteronymous excitation magnitude in the paretic limb was positively correlated with self-selected walking speed suggesting paretic limb excitation at the higher end of a normal range may facilitate walking ability after stroke. Future studies are needed to identify whether heteronymous feedback from Q onto SOL is altered after stroke in upright postures and during motor tasks as a necessary next step to identify mechanisms underlying motor impairment.

Examination of acute spin exercise on GABA levels in aging and stroke: The EASE study protocol.

BACKGROUND: Changes in regional levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may indicate the potential for favorable responses to the treatment of stroke affecting the upper extremity. By selectively altering GABA levels during training, we may induce long-term potentiation and adjust excitatory/inhibitory balance (E/I balance). However, the impact of this alteration may be limited by neural damage or aging. Aerobic exercise has been shown to increase GABA levels in the sensorimotor cortex and improve motor learning by widening the dynamic range of E/I balance. The cross-sectional project, Effects of Acute Exercise on Functional Magnetic Resonance Spectroscopy Measures of GABA in Aging and Chronic Stroke (EASE), is designed to assess the functional relevance of changes in GABA concentration within the sensorimotor cortex before and after an acute aerobic exercise session. METHODS/DESIGN: EASE will enroll 30 participants comprised of healthy younger adults (18-35 years; n = 10), older adults (60+ years; n = 10), and persons with chronic stroke (n = 10) affecting distal upper extremity function. We will use resting magnetic resonance spectroscopy to measure all participants' GABA levels at rest before and after aerobic exercise. In addition, we will employ functional magnetic resonance spectroscopy using motor skill acquisition and recall tasks in healthy adults. We hypothesize that acute aerobic exercise will increase resting sensorimotor GABA concentration and that higher GABA resting levels will predict better motor learning performance on measures taken both inside and outside the magnet. We also hypothesize that a higher dynamic range of GABA during task-based spectroscopy in healthy adults will predict better motor skill acquisition and recall. DISCUSSION: The EASE project will evaluate the effect of acute exercise on GABA levels as a biomarker of upper extremity motor skill learning with two populations (aging adults and those with chronic stroke). We predict that acute exercise, higher sensorimotor GABA levels, and broader dynamic range will be related to better motor skill acquisition.

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.

Reduced inhibition from quadriceps onto soleus after acute quadriceps fatigue suggests Golgi tendon organ contribution to heteronymous inhibition.

Heteronymous inhibition between lower limb muscles is primarily attributed to recurrent inhibitory circuits in humans but could also arise from Golgi tendon organs (GTOs). Distinguishing between recurrent inhibition and mechanical activation of GTOs is challenging because their heteronymous effects are both elicited by stimulation of nerves or a muscle above motor threshold. Here, the unique influence of mechanically activated GTOs was examined by comparing the magnitude of heteronymous inhibition from quadriceps (Q) muscle stimulation onto ongoing soleus electromyographic at five Q stimulation intensities (1.5-2.5× motor threshold) before and after an acute bout of stimulation-induced Q fatigue. Fatigue was used to decrease Q stimulation evoked force (i.e., decreased GTO activation) despite using the same pre-fatigue stimulation currents (i.e., same antidromic recurrent inhibition input). Thus, a decrease in heteronymous inhibition after Q fatigue and a linear relation between stimulation-evoked torque and inhibition both before and after fatigue would support mechanical activation of GTOs as a source of inhibition. A reduction in evoked torque but no change in inhibition would support recurrent inhibition. After fatigue, Q stimulation-evoked knee torque, heteronymous inhibition magnitude and inhibition duration were significantly decreased for all stimulation intensities. In addition, heteronymous inhibition magnitude was linearly related to twitch-evoked knee torque before and after fatigue. These findings support mechanical activation of GTOs as a source of heteronymous inhibition along with recurrent inhibition. The unique patterns of heteronymous inhibition before and after fatigue across participants suggest the relative contribution of GTOs, and recurrent inhibition may vary across persons.

Distal Versus Proximal Arm Improvement After Paired Vagus Nerve Stimulation Therapy After Chronic Stroke.

OBJECTIVE: To evaluate differences in upper-extremity (UE) segment-specific (proximal or distal segment) recovery after vagus nerve stimulation (VNS) paired with UE rehabilitation (Paired-VNS) compared with rehabilitation with sham-VNS (Control). We also assessed whether gains in specific UE segments predicted clinically meaningful improvement. DESIGN: This study reports on a secondary analysis of Vagus nerve stimulation paired with rehabilitation for UE motor function after chronic ischemic stroke (VNS-REHAB), a randomized, triple-blinded, sham-controlled pivotal trial. A Rasch latent regression was used to determine differences between Paired-VNS and Controls for distal and proximal UE changes after in-clinic therapy and 3 months later. Subsequently, we ran a random forest model to assess candidate predictors of meaningful improvement. Each item of the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) was evaluated as a predictor of response to treatment. SETTING: Nineteen stroke rehabilitation centers in the USA and UK. PARTICIPANTS: Dataset included 108 participants (N=108) with chronic ischemic stroke and moderate-to-severe UE impairments. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FMA-UE and WMFT. RESULTS: Distal UE improvement was significantly greater in the Paired-VNS group than in Controls immediately after therapy (95% confidence interval, 0.27-0.73; P≤.001) and after 3 months (95% confidence interval, 0.16-0.75; P=.003). Both groups showed similar improvement in proximal UE at both time points. A subset of both distal and proximal items from the FMA-UE and WMFT were predictors of meaningful improvement. CONCLUSIONS: Paired-VNS improved distal UE impairment in chronic stroke to a greater degree than intensive rehabilitation alone. Proximal improvements were equally responsive to either treatment. Given that meaningful UE recovery is predicted by improvements across both proximal and distal segments, Paired-VNS may facilitate improvement that is otherwise elusive.

Comparison of externally and internally guided dance movement to address mobility, cognition, and psychosocial function in people with Parkinson's disease and freezing of gait: a case series.

Objective: The aim of this study is to explore the impact of internally guided (IG) versus externally guided (EG) adapted tango (AT) dance training (i.e., dancing the IG "Leader" role or the EG "Follower" role), on motor and non-motor functions in individuals with Parkinson's disease and freezing of gait (PD-FOG). The "Leader" role, a proxy for IG movements, conveys direction, timing, and amplitude of steps with tactile cues. The "Follower" role, a proxy for EG movements, detects and responds to the leader's tactile cues. Case description: Six participants were randomly assigned to the IG ("Leader") or EG ("Follower") roles for 20, 90-min AT lessons over 12 weeks. Participants were assessed for PD-specific and non-PD-specific functions before and twice after the end of the 12-week intervention, at 1-week and 1-month post-intervention. Results: EG participants improved and/or maintained performance on more outcomes across all domains than IG participants. Five participants improved in PD motor symptoms, dynamic gait, global cognitive function, and the FOG Questionnaire immediately or 1 month after intervention. All participants expressed positive attitudes toward the intervention, including improvements in walking, balance, and endurance. Conclusion: AT training in the follower role may benefit individuals with PD-FOG to a greater extent compared to the leader role. Impact: This case series study could inform additional research with the goal of enhancing physical therapy or music-based therapy approaches for addressing PD-FOG.

Differential effect of heteronymous feedback from femoral nerve and quadriceps muscle stimulation onto soleus H-reflex.

Excitatory feedback from muscle spindles, and inhibitory feedback from Golgi tendon organs and recurrent inhibitory circuits are widely distributed within the spinal cord to modulate activity between human lower limb muscles. Heteronymous feedback is most commonly studied in humans by stimulating peripheral nerves, but the unique effect of non-spindle heteronymous feedback is difficult to determine due to the lower threshold of excitatory spindle axons. A few studies suggest stimulation of the muscle belly preferentially elicits non-spindle heteronymous feedback. However, there remains a lack of consensus on the differential effect of nerve and muscle stimulation onto the H-reflex, and the relation of the heteronymous effects onto H-reflex compared to that onto ongoing EMG has not been determined. In this cross-sectional study, we compared excitatory and inhibitory effects from femoral nerve and quadriceps muscle belly stimulation onto soleus H-reflex size in 15 able-bodied participants and in a subset also compared heteronymous effects onto ongoing soleus EMG at 10% and 20% max. Femoral nerve stimulation elicited greater excitation of the H-reflex compared to quadriceps stimulation. The differential effect was also observed onto ongoing soleus EMG at 20% max but not 10%. Femoral nerve and quadriceps stimulation elicited similar inhibition of the soleus H-reflexes, and these results were better associated with soleus EMG at 20%. The results support surface quadriceps muscles stimulation as a method to preferentially study heteronymous inhibition at least in healthy adults. The primary benefit of using muscle stimulation is expected to be in persons with abnormal, prolonged heteronymous excitation. These data further suggest heteronymous feedback should be evaluated with H-reflex or onto ongoing EMG of at least 20% max to identify group differences or modulation of heteronymous feedback in response to treatment or task.

Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial.

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1-3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .

Perceptions of stroke survivors regarding factors affecting adoption of technology and exergames for rehabilitation.

BACKGROUND: Task-specific motor training and repetitive practice are essential components of clinical rehabilitation. Emerging evidence suggests that incorporating gaming interfaces (also referred to as "exergames"), including virtual reality and augmented reality (VR/AR)-based interfaces for motor training, can enhance the engagement and efficacy of poststroke rehabilitation. OBJECTIVE: To investigate perceptions of individuals with stroke regarding technology and exergames for rehabilitation. DESIGN: This qualitative phenomenological study included a convenience sample of 11 individuals with stroke (61.7 ± 12.4 years, 6 women and 5 men, 63.5 ± 41.2 months post stroke). SETTING: Community. INTERVENTIONS: N/A. OUTCOME MEASURES: Semistructured open-ended focus-group interviews to understand their perceptions on technology and exergames to improve recovery were coded using thematic content analysis. RESULTS: Individuals with stroke were comfortable using smartphones, computers, and rehabilitation technologies but had limited experiences using exergames and VR/AR devices. Individuals with stroke were motivated to use technologies and exergames to improve their functional recovery. Participants identified facilitators (eg, enhancing functional recovery, feedback, therapist supervision) and barriers (eg, safety, inaccessibility, inadequate knowledge) to adopting exergames in their daily lives. Participants wanted the exergames to be customizable, goal oriented, and enjoyable to maintain their engagement. They were willing to use exergames to improve their functional recovery but indicated that these games could not replace the therapist's supervision. CONCLUSIONS: Despite having limited experiences with exergames, people post stroke perceived that exergames could promote functional recovery. The perspectives gained from the present study can inform user-centered game design for neurorehabilitation.

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial.

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke. OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury. METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS treatment by sex, age (≥62 years), time from stroke (>2 years), severity (baseline FMA-UE score >34), paretic side of body, country of enrollment (USA vs UK) and presence of cortical involvement of the index infarction. We assessed whether there was any interaction with treatment. FINDINGS: The primary outcome increased by 5.0 points (SD 4.4) in the VNS group and by 2.4 points (SD 3.8) in the Control group (P = .001, between group difference 2.6, 95% CI 1.03-4.2). The between group difference was similar across all subgroups and there were no significant treatment interactions. There was no important difference in rates of adverse events across subgroups. CONCLUSION: The response was similar across subgroups examined. The findings suggest that the effects of paired VNS observed in the VNS-REHAB trial are likely to be consistent in wide range of stroke survivors with moderate to severe upper extremity impairment.

Quadriceps muscle stimulation evokes heteronymous inhibition onto soleus with limited Ia activation compared to femoral nerve stimulation.

Heteronymous excitatory feedback from muscle spindles and inhibitory feedback from Golgi tendon organs and recurrent inhibitory circuits can influence motor coordination. The functional role of inhibitory feedback is difficult to determine, because nerve stimulation, the primary method used in humans, cannot evoke inhibition without first activating the largest diameter muscle spindle axons. Here, we tested the hypothesis that quadriceps muscle stimulation could be used to examine heteronymous inhibition more selectively when compared to femoral nerve stimulation by comparing the effects of nerve and muscle stimulation onto ongoing soleus EMG held at 20% of maximal effort. Motor threshold and two higher femoral nerve and quadriceps stimulus intensities matched by twitch evoked torque magnitudes were examined. We found that significantly fewer participants exhibited excitation during quadriceps muscle stimulation when compared to nerve stimulation (14-29% vs. 64-71% of participants across stimulation intensities) and the magnitude of heteronymous excitation from muscle stimulation, when present, was much reduced compared to nerve stimulation. Muscle and nerve stimulation resulted in heteronymous inhibition that significantly increased with increasing stimulation evoked torque magnitudes. This study provides novel evidence that muscle stimulation may be used to more selectively examine inhibitory heteronymous feedback between muscles in the human lower limb when compared to nerve stimulation.

Repetitive Transcranial Magnetic Stimulation of the Contralesional Dorsal Premotor Cortex for Upper Extremity Motor Improvement in Severe Stroke: Study Protocol for a Pilot Randomized Clinical Trial.

Up to 50% of stroke survivors have persistent, severe upper extremity paresis even after receiving rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) can augment the effects of rehabilitation by modulating corticomotor excitability, but the conventional approach of facilitating excitability of the ipsilesional primary motor cortex (iM1) fails to produce motor improvement in stroke survivors with severe loss of ipsilesional substrate. Instead, the undamaged, contralesional dorsal premotor cortex (cPMd) may be a more suitable target. CPMd can offer alternate, bi-hemispheric and ipsilateral connections in support of paretic limb movement. This pilot, randomized clinical trial seeks to investigate whether rTMS delivered to facilitate cPMd in conjunction with rehabilitation produces greater gains in motor function than conventional rTMS delivered to facilitate iM1 in conjunction with rehabilitation in severely impaired stroke survivors. Twenty-four chronic (≥6 months) stroke survivors with severe loss of ipsilesional substrate (defined by the absence of physiologic evidence of excitable residual pathways tested using TMS) will be included. Participants will be randomized to receive rTMS to facilitate cPMd or iM1 in conjunction with task-oriented upper limb rehabilitation given for 2 sessions/week for 6 weeks. Assessments of primary outcome related to motor impairment (upper extremity Fugl-Meyer [UEFM]), motor function, neurophysiology, and functional neuroimaging will be made at baseline and at 6-week end-of-treatment. An additional assessment of motor outcomes will be repeated at 3-month follow-up to evaluate retention. The primary endpoint is 6-week change in UEFM. This pilot trial will provide preliminary evidence on the effects and mechanisms associated with facilitating intact cPMd in chronic severe stroke survivors. The trial is registered on clinicaltrials.gov, NCT03868410.

Genetic Factors, Brain Atrophy, and Response to Rehabilitation Therapy After Stroke.

OBJECTIVE: Patients show substantial differences in response to rehabilitation therapy after stroke. We hypothesized that specific genetic profiles might explain some of this variance and, secondarily, that genetic factors are related to cerebral atrophy post-stroke. METHODS: The phase 3 ICARE study examined response to motor rehabilitation therapies. In 216 ICARE enrollees, DNA was analyzed for presence of the BDNF val66met and the ApoE ε4 polymorphism. The relationship of polymorphism status to 12-month change in motor status (Wolf Motor Function Test, WMFT) was examined. Neuroimaging data were also evaluated (n=127). RESULTS: Subjects were 61±13 years old (mean±SD) and enrolled 43±22 days post-stroke; 19.7% were BDNF val66met carriers and 29.8% ApoE ε4 carriers. Carrier status for each polymorphism was not associated with WMFT, either at baseline or over 12 months of follow-up. Neuroimaging, acquired 5±11 days post-stroke, showed that BDNF val66met polymorphism carriers had a 1.34-greater degree of cerebral atrophy compared to non-carriers (P=.01). Post hoc analysis found that age of stroke onset was 4.6 years younger in subjects with the ApoE ε4 polymorphism (P=.02). CONCLUSION: Neither the val66met BDNF nor ApoE ε4 polymorphism explained inter-subject differences in response to rehabilitation therapy. The BDNF val66met polymorphism was associated with cerebral atrophy at baseline, echoing findings in healthy subjects, and suggesting an endophenotype. The ApoE ε4 polymorphism was associated with younger age at stroke onset, echoing findings in Alzheimer's disease and suggesting a common biology. Genetic associations provide insights useful to understanding the biology of outcomes after stroke.

Motor Cortical Network Flexibility is Associated With Biomechanical Walking Impairment in Chronic Stroke.

Background: The inability to flexibly modulate motor behavior with changes in task demand or environmental context is a pervasive feature of motor impairment and dysfunctional mobility after stroke. Objective: The purpose of this study was to test the reactive and modulatory capacity of lower-limb primary motor cortical (M1) networks using electroencephalography (EEG) measures of cortical activity evoked by transcranial magnetic stimulation (TMS) and to evaluate their associations with clinical and biomechanical measures of walking function in chronic stroke. Methods: TMS assessments of motor cortex excitability were performed during rest and active ipsilateral plantarflexion in chronic stroke and age-matched controls. TMS-evoked motor cortical network interactions were quantified with simultaneous EEG as the post-TMS (0-300 ms) beta (15-30 Hz) coherence between electrodes overlying M1 bilaterally. We compared TMS-evoked coherence between groups during rest and active conditions and tested associations with poststroke motor impairment, paretic propulsive gait deficits, and the presence of paretic leg motor evoked potentials (MEPs). Results: Stroke (n = 14, 66 ± 9 years, F = 4) showed lower TMS-evoked cortical coherence and activity-dependent modulation compared to controls (n = 9, 68 ± 6 years, F = 3). Blunted reactivity and atypical modulation of TMS-evoked coherence were associated with lower paretic ankle moments for propulsive force generation during walking and absent paretic MEPs. Conclusions: Impaired flexibility of motor cortical networks to react to TMS and modulate during motor activity is distinctly associated with paretic limb biomechanical walking impairment, and may provide useful insight into the neuromechanistic underpinnings of chronic post-stroke mobility deficits.

Automated Movement Assessment in Stroke Rehabilitation.

We are developing a system for long term Semi-Automated Rehabilitation At the Home (SARAH) that relies on low-cost and unobtrusive video-based sensing. We present a cyber-human methodology used by the SARAH system for automated assessment of upper extremity stroke rehabilitation at the home. We propose a hierarchical model for automatically segmenting stroke survivor's movements and generating training task performance assessment scores during rehabilitation. The hierarchical model fuses expert therapist knowledge-based approaches with data-driven techniques. The expert knowledge is more observable in the higher layers of the hierarchy (task and segment) and therefore more accessible to algorithms incorporating high level constraints relating to activity structure (i.e., type and order of segments per task). We utilize an HMM and a Decision Tree model to connect these high level priors to data driven analysis. The lower layers (RGB images and raw kinematics) need to be addressed primarily through data driven techniques. We use a transformer based architecture operating on low-level action features (tracking of individual body joints and objects) and a Multi-Stage Temporal Convolutional Network(MS-TCN) operating on raw RGB images. We develop a sequence combining these complimentary algorithms effectively, thus encoding the information from different layers of the movement hierarchy. Through this combination, we produce a robust segmentation and task assessment results on noisy, variable and limited data, which is characteristic of low cost video capture of rehabilitation at the home. Our proposed approach achieves 85% accuracy in per-frame labeling, 99% accuracy in segment classification and 93% accuracy in task completion assessment. Although the methodology proposed in this paper applies to upper extremity rehabilitation using the SARAH system, it can potentially be used, with minor alterations, to assist automation in many other movement rehabilitation contexts (i.e., lower extremity training for neurological accidents).

Clinical Performance Measures for Stroke Rehabilitation: Performance Measures From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released the adult stroke rehabilitation and recovery guidelines in 2016. A working group of stroke rehabilitation experts reviewed these guidelines and identified a subset of recommendations that were deemed suitable for creating performance measures. These 13 performance measures are reported here and contain inclusion and exclusion criteria to allow calculation of rates of compliance in a variety of settings ranging from acute hospital care to postacute care and care in the home and outpatient setting.

Biofeedback for Post-stroke Gait Retraining: A Review of Current Evidence and Future Research Directions in the Context of Emerging Technologies.

Real-time gait biofeedback is a promising rehabilitation strategy for improving biomechanical deficits in walking patterns of post-stroke individuals. Because wearable sensor technologies are creating avenues for novel applications of gait biofeedback, including use in tele-health, there is a need to evaluate the state of the current evidence regarding the effectiveness of biofeedback for post-stroke gait training. The objectives of this review are to: (1) evaluate the current state of biofeedback literature pertaining to post-stroke gait training; and (2) determine future research directions related to gait biofeedback in context of evolving technologies. Our overall goal was to determine whether gait biofeedback is effective at improving stroke gait deficits while also probing why and for whom gait biofeedback may be an efficacious treatment modality. Our literature review showed that the effects of gait biofeedback on post-stroke walking dysfunction are promising but are inconsistent in methodology and therefore results. We summarize sources of methodological heterogeneity in previous literature, such as inconsistencies in feedback target, feedback mode, dosage, practice structure, feedback structure, and patient characteristics. There is a need for larger-sample studies that directly compare different feedback parameters, employ more uniform experimental designs, and evaluate characteristics of potential responders. However, as these uncertainties in existing literature are resolved, the application of gait biofeedback has potential to extend neurorehabilitation clinicians' cues to individuals with post-stroke gait deficits during ambulation in clinical, home, and community settings, thereby increasing the quantity and quality of skilled repetitions during task-oriented stepping training. In addition to identifying gaps in previous research, we posit that future research directions should comprise an amalgam of mechanism-focused and clinical research studies, to develop evidence-informed decision-making guidelines for gait biofeedback strategies that are tailored to individual-specific gait and sensorimotor impairments. Wearable sensor technologies have the potential to transform gait biofeedback and provide greater access and wider array of options for clinicians while lowering rehabilitation costs. Novel sensing technologies will be particularly valuable for telehealth and home-based stepping exercise programs. In summary, gait biofeedback is a promising intervention strategy that can enhance efficacy of post-stroke gait rehabilitation in both clinical and tele-rehabilitation settings and warrants more in-depth research.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.

A First Step Toward the Operationalization of the Learned Non-Use Phenomenon: A Delphi Study.

BACKGROUND: The negative discrepancy between residual functional capacity and reduced use of the contralesional hand, frequently observed after a brain lesion, has been termed Learned Non-Use (LNU) and is thought to depend on the interaction of neuronal mechanisms during recovery and learning-dependent mechanisms. OBJECTIVE: Albeit the LNU phenomenon is generally accepted to exist, currently, no transdisciplinary definition exists. Furthermore, although therapeutic approaches are implemented in clinical practice targeting LNU, no standardized diagnostic routine is described in the available literature. Our objective was to reach consensus regarding a definition as well as synthesize knowledge about the current diagnostic procedures. METHODS: We used a structured group communication following the Delphi method among clinical and scientific experts in the field, knowledge from both, the work with patient populations and with animal models. RESULTS: Consensus was reached regarding a transdisciplinary definition of the LNU phenomenon. Furthermore, the mode and strategy of the diagnostic process, as well as the sources of information and outcome parameters relevant for the clinical decision making, were described with a wide range showing the current lack of a consistent universal diagnostic approach. CONCLUSIONS: The need for the development of a structured diagnostic procedure and its implementation into clinical practice is emphasized. Moreover, it exists a striking gap between the prevailing hypotheses regarding the mechanisms underlying the LNU phenomenon and the actual evidence. Therefore, basic research is needed to bridge between bedside and bench and eventually improve clinical decision making and further development of interventional strategies beyond the field of stroke rehabilitation.