A single-center, assessor-blinded, randomized controlled clinical trial to test the safety and efficacy of a novel brain-computer interface controlled functional electrical stimulation (BCI-FES) intervention for gait rehabilitation in the chronic stroke population.

BACKGROUND: In the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise in early feasibility studies. The current study describes the BCI-FES clinical trial, which examines the safety and efficacy of this system, compared to conventional physical therapy (PT), to improve gait velocity for those with chronic gait impairment post-stroke. The trial also aims to find other secondary factors that may impact or accompany these improvements and establish the potential of Hebbian-based rehabilitation therapies. METHODS: This Phase II clinical trial is a two-arm, randomized, controlled, longitudinal study with 66 stroke participants in the chronic (> 6 months) stage of gait impairment. The participants undergo either BCI-FES paired with PT or dose-matched PT sessions (three times weekly for four weeks). The primary outcome is gait velocity (10-meter walk test), and secondary outcomes include gait endurance, range of motion, strength, sensation, quality of life, and neurophysiological biomarkers. These measures are acquired longitudinally. DISCUSSION: BCI-FES holds promise for gait velocity improvements in stroke patients. This clinical trial will evaluate the safety and efficacy of BCI-FES therapy when compared to dose-matched conventional therapy. The success of this trial will inform the potential utility of a Phase III efficacy trial. TRIAL REGISTRATION: The trial was registered as "BCI-FES Therapy for Stroke Rehabilitation" on February 19, 2020, at clinicaltrials.gov with the identifier NCT04279067.

Social Network Structure Is Related to Functional Improvement From Home-Based Telerehabilitation After Stroke.

Objective: Telerehabilitation (TR) is now, in the context of COVID-19, more clinically relevant than ever as a major source of outpatient care. The social network of a patient is a critical yet understudied factor in the success of TR that may influence both engagement in therapy programs and post-stroke outcomes. We designed a 12-week home-based TR program for stroke patients and evaluated which social factors might be related to motor gains and reduced depressive symptoms. Methods: Stroke patients (n = 13) with arm motor deficits underwent supervised home-based TR for 12 weeks with routine assessments of motor function and mood. At the 6-week midpoint, we mapped each patient's personal social network and evaluated relationships between social network metrics and functional improvements from TR. Finally, we compared social networks of TR patients with a historical cohort of 176 stroke patients who did not receive any TR to identify social network differences. Results: Both network size and network density were related to walk time improvement (p = 0.025; p = 0.003). Social network density was related to arm motor gains (p = 0.003). Social network size was related to reduced depressive symptoms (p = 0.015). TR patient networks were larger (p = 0.012) and less dense (p = 0.046) than historical stroke control networks. Conclusions: Social network structure is positively related to improvement in motor status and mood from TR. TR patients had larger and more open social networks than stroke patients who did not receive TR. Understanding how social networks intersect with TR outcomes is crucial to maximize effects of virtual rehabilitation.

Intense Arm Rehabilitation Therapy Improves the Modified Rankin Scale Score: Association Between Gains in Impairment and Function.

OBJECTIVE: To evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains. METHODS: Patients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm. Activity gains, measured using the mRS, were examined and compared to body structure/function gains, measured using the Fugl-Meyer (FM) motor scale. Additional analyses examined whether activity gains were more strongly related to specific body structure/function gains. RESULTS: At baseline (160 ± 48 days poststroke), patients (n = 77) had median mRS score of 3 (interquartile range, 2-3), decreasing to 2 [2-3] 30 days posttherapy (p < 0.0001). Similarly, the proportion of patients with mRS score ≤2 increased from 46.8% at baseline to 66.2% at 30 days posttherapy (p = 0.015). These findings were accounted for by the mRS score decreasing in 24 (31.2%) patients. Patients with a treatment-related mRS score improvement, compared to those without, had similar overall motor gains (change in total FM score, p = 0.63). In exploratory analysis, improvement in several specific motor impairments, such as finger flexion and wrist circumduction, was significantly associated with higher likelihood of mRS decrease. CONCLUSIONS: Intensive arm motor therapy is associated with improved mRS in a substantial fraction (31.2%) of patients. Exploratory analysis suggests specific motor impairments that might underlie this finding and may be optimal targets for rehabilitation therapies that aim to reduce activities limitations. CLINICAL TRIAL: Clinicaltrials.gov identifier: NCT02360488. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients >90 days poststroke with persistent arm motor deficits, intensive arm motor therapy improved mRS in a substantial fraction (31.2%) of patients.

Gains Across WHO Dimensions of Function After Robot-Based Therapy in Stroke Subjects.

BACKGROUND: Studies examining the effects of therapeutic interventions after stroke often focus on changes in loss of body function/structure (impairment). However, improvements in activities limitations and participation restriction are often higher patient priorities, and the relationship that these measures have with loss of body function/structure is unclear. OBJECTIVE: This study measured gains across WHO International Classification of Function (ICF) dimensions and examined their interrelationships. METHODS: Subjects were recruited 11 to 26 weeks after hemiparetic stroke. Over a 3-week period, subjects received 12 sessions of intensive robot-based therapy targeting the distal arm. Each subject was assessed at baseline and at 1 month after end of therapy. RESULTS: At baseline, subjects (n = 40) were 134.7 ± 32.4 (mean ± SD) days poststroke and had moderate-severe arm motor deficits (arm motor Fugl-Meyer score of 35.6 ± 14.4) that were stable. Subjects averaged 2579 thumb movements and 1298 wrist movements per treatment session. After robot therapy, there was significant improvement in measures of body function/structure (Fugl-Meyer score) and activity limitations (Action Research Arm Test, Barthel Index, and Stroke Impact Scale-Hand), but not participation restriction (Stroke Specific Quality of Life Scale). Furthermore, while the degree of improvement in loss of body function/structure was correlated with improvement in activity limitations, neither improvement in loss of body function/structure nor improvement in activity limitations was correlated with change in participation restriction. CONCLUSIONS: After a 3-week course of robotic therapy, there was improvement in body function/structure and activity limitations but no reduction in participation restriction.

A Feasibility Study of Expanded Home-Based Telerehabilitation After Stroke.

Introduction: High doses of activity-based rehabilitation therapy improve outcomes after stroke, but many patients do not receive this for various reasons such as poor access, transportation difficulties, and low compliance. Home-based telerehabilitation (TR) can address these issues. The current study evaluated the feasibility of an expanded TR program. Methods: Under the supervision of a licensed therapist, adults with stroke and limb weakness received home-based TR (1 h/day, 6 days/week) delivered using games and exercises. New features examined include extending therapy to 12 weeks duration, treating both arm and leg motor deficits, patient assessments performed with no therapist supervision, adding sensors to real objects, ingesting a daily experimental (placebo) pill, and generating automated actionable reports. Results: Enrollees (n = 13) were median age 61 (IQR 52-65.5), and 129 (52-486) days post-stroke. Patients initiated therapy on 79.9% of assigned days and completed therapy on 65.7% of days; median therapy dose was 50.4 (33.3-56.7) h. Non-compliance doubled during weeks 7-12. Modified Rankin scores improved in 6/13 patients, 3 of whom were >3 months post-stroke. Fugl-Meyer motor scores increased by 6 (2.5-12.5) points in the arm and 1 (-0.5 to 5) point in the leg. Assessments spanning numerous dimensions of stroke outcomes were successfully implemented; some, including a weekly measure that documented a decline in fatigue (p = 0.004), were successfully scored without therapist supervision. Using data from an attached sensor, real objects could be used to drive game play. The experimental pill was taken on 90.9% of therapy days. Automatic actionable reports reliably notified study personnel when critical values were reached. Conclusions: Several new features performed well, and useful insights were obtained for those that did not. A home-based telehealth system supports a holistic approach to rehabilitation care, including intensive rehabilitation therapy, secondary stroke prevention, screening for complications of stroke, and daily ingestion of a pill. This feasibility study informs future efforts to expand stroke TR. Clinical Trial Registration: Clinicaltrials.gov, # NCT03460587.

A qualitative study on user acceptance of a home-based stroke telerehabilitation system.

Objective: This paper reports a qualitative study of a home-based stroke telerehabilitation system. The telerehabilitation system delivers treatment sessions in the form of daily guided rehabilitation games, exercises, and stroke education in the patient's home. The aims of the current report are to investigate patient perceived benefits of and barriers to using the telerehabilitation system at home.Methods: We used a qualitative study design that involved in-depth semi-structured interviews with 13 participants who were patients in the subacute phase after stroke and had completed a six-week intervention using the home-based telerehabilitation system. Thematic analysis was conducted to analyze the data.Results: Participants mostly reported positive experiences with the telerehabilitation system. Benefits included observed improvements in limb functions, cognitive abilities, and emotional well-being. They also perceived the system easy to use due to the engaging experience and the convenience of conducting sessions at home. Meanwhile, participants pointed out the importance of considering technical support and physical environment at home. Further, family members' support helped them sustain in their rehabilitation. Finally, adjusting difficulty levels and visualizing patients' rehabilitation progress might help them in continued use of the telerehabilitation system.Conclusion: Telerehabilitation systems can be used as an efficient and user-friendly tool to deliver home-based stroke rehabilitation that enhance patients' physical recovery and mental and social-emotional wellbeing. Such systems need to be designed to offer engaging experience, display of recovery progress, and flexibility of schedule and location, with consideration of facilitating and social factors.

Efficacy of Home-Based Telerehabilitation vs In-Clinic Therapy for Adults After Stroke: A Randomized Clinical Trial.

IMPORTANCE: Many patients receive suboptimal rehabilitation therapy doses after stroke owing to limited access to therapists and difficulty with transportation, and their knowledge about stroke is often limited. Telehealth can potentially address these issues. OBJECTIVES: To determine whether treatment targeting arm movement delivered via a home-based telerehabilitation (TR) system has comparable efficacy with dose-matched, intensity-matched therapy delivered in a traditional in-clinic (IC) setting, and to examine whether this system has comparable efficacy for providing stroke education. DESIGN, SETTING, AND PARTICIPANTS: In this randomized, assessor-blinded, noninferiority trial across 11 US sites, 124 patients who had experienced stroke 4 to 36 weeks prior and had arm motor deficits (Fugl-Meyer [FM] score, 22-56 of 66) were enrolled between September 18, 2015, and December 28, 2017, to receive telerehabilitation therapy in the home (TR group) or therapy at an outpatient rehabilitation therapy clinic (IC group). Primary efficacy analysis used the intent-to-treat population. INTERVENTIONS: Participants received 36 sessions (70 minutes each) of arm motor therapy plus stroke education, with therapy intensity, duration, and frequency matched across groups. MAIN OUTCOMES AND MEASURES: Change in FM score from baseline to 4 weeks after end of therapy and change in stroke knowledge from baseline to end of therapy. RESULTS: A total of 124 participants (34 women and 90 men) had a mean (SD) age of 61 (14) years, a mean (SD) baseline FM score of 43 (8) points, and were enrolled a mean (SD) of 18.7 (8.9) weeks after experiencing a stroke. Among those treated, patients in the IC group were adherent to 33.6 of the 36 therapy sessions (93.3%) and patients in the TR group were adherent to 35.4 of the 36 assigned therapy sessions (98.3%). Patients in the IC group had a mean (SD) FM score change of 8.36 (7.04) points from baseline to 30 days after therapy (P < .001), while those in the TR group had a mean (SD) change of 7.86 (6.68) points (P < .001). The covariate-adjusted mean FM score change was 0.06 (95% CI, -2.14 to 2.26) points higher in the TR group (P = .96). The noninferiority margin was 2.47 and fell outside the 95% CI, indicating that TR is not inferior to IC therapy. Motor gains remained significant when patients enrolled early (<90 days) or late (≥90 days) after stroke were examined separately. CONCLUSIONS AND RELEVANCE: Activity-based training produced substantial gains in arm motor function regardless of whether it was provided via home-based telerehabilitation or traditional in-clinic rehabilitation. The findings of this study suggest that telerehabilitation has the potential to substantially increase access to rehabilitation therapy on a large scale. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02360488.

Predicting Gains With Visuospatial Training After Stroke Using an EEG Measure of Frontoparietal Circuit Function.

The heterogeneity of stroke prompts the need for predictors of individual treatment response to rehabilitation therapies. We previously studied healthy subjects with EEG and identified a frontoparietal circuit in which activity predicted training-related gains in visuomotor tracking. Here we asked whether activity in this same frontoparietal circuit also predicts training-related gains in visuomotor tracking in patients with chronic hemiparetic stroke. Subjects (n = 12) underwent dense-array EEG recording at rest, then received 8 sessions of visuomotor tracking training delivered via home-based telehealth methods. Subjects showed significant training-related gains in the primary behavioral endpoint, Success Rate score on a standardized test of visuomotor tracking, increasing an average of 24.2 ± 21.9% (p = 0.003). Activity in the circuit of interest, measured as coherence (20-30 Hz) between leads overlying ipsilesional frontal (motor cortex) and parietal lobe, significantly predicted training-related gains in visuomotor tracking change, measured as change in Success Rate score (r = 0.61, p = 0.037), supporting the main study hypothesis. Results were specific to the hypothesized ipsilesional motor-parietal circuit, as coherence within other circuits did not predict training-related gains. Analyses were repeated after removing the four subjects with injury to motor or parietal areas; this increased the strength of the association between activity in the circuit of interest and training-related gains. The current study found that (1) Eight sessions of training can significantly improve performance on a visuomotor task in patients with chronic stroke, (2) this improvement can be realized using home-based telehealth methods, (3) an EEG-based measure of frontoparietal circuit function predicts training-related behavioral gains arising from that circuit, as hypothesized and with specificity, and (4) incorporating measures of both neural function and neural injury improves prediction of stroke rehabilitation therapy effects.

Biomarkers of Rehabilitation Therapy Vary according to Stroke Severity.

Biomarkers that capture treatment effects could improve the precision of clinical decision making for restorative therapies. We examined the performance of candidate structural, functional, and angiogenesis-related MRI biomarkers before and after a 3-week course of standardized robotic therapy in 18 patients with chronic stroke and hypothesized that results vary significantly according to stroke severity. Patients were 4.1 ± 1 months poststroke, with baseline arm Fugl-Meyer scores of 20-60. When all patients were examined together, no imaging measure changed over time in a manner that correlated with treatment-induced motor gains. However, when also considering the interaction with baseline motor status, treatment-induced motor gains were significantly related to change in three functional connectivity measures: ipsilesional motor cortex connectivity with (1) contralesional motor cortex (p = 0.003), (2) contralesional dorsal premotor cortex (p = 0.005), and (3) ipsilesional dorsal premotor cortex (p = 0.004). In more impaired patients, larger treatment gains were associated with greater increases in functional connectivity, whereas in less impaired patients larger treatment gains were associated with greater decreases in functional connectivity. Functional connectivity measures performed best as biomarkers of treatment effects after stroke. The relationship between changes in functional connectivity and treatment gains varied according to baseline stroke severity. Biomarkers of restorative therapy effects are not one-size-fits-all after stroke.

A Home-Based Telerehabilitation Program for Patients With Stroke.

BACKGROUND: Although rehabilitation therapy is commonly provided after stroke, many patients do not derive maximal benefit because of access, cost, and compliance. A telerehabilitation-based program may overcome these barriers. We designed, then evaluated a home-based telerehabilitation system in patients with chronic hemiparetic stroke. METHODS: Patients were 3 to 24 months poststroke with stable arm motor deficits. Each received 28 days of telerehabilitation using a system delivered to their home. Each day consisted of 1 structured hour focused on individualized exercises and games, stroke education, and an hour of free play. RESULTS: Enrollees (n = 12) had baseline Fugl-Meyer (FM) scores of 39 ± 12 (mean ± SD). Compliance was excellent: participants engaged in therapy on 329/336 (97.9%) assigned days. Arm repetitions across the 28 days averaged 24,607 ± 9934 per participant. Arm motor status showed significant gains (FM change 4.8 ± 3.8 points, P = .0015), with half of the participants exceeding the minimal clinically important difference. Although scores on tests of computer literacy declined with age ( r = -0.92; P < .0001), neither the motor gains nor the amount of system use varied with computer literacy. Daily stroke education via the telerehabilitation system was associated with a 39% increase in stroke prevention knowledge ( P = .0007). Depression scores obtained in person correlated with scores obtained via the telerehabilitation system 16 days later ( r = 0.88; P = .0001). In-person blood pressure values closely matched those obtained via this system ( r = 0.99; P < .0001). CONCLUSIONS: This home-based system was effective in providing telerehabilitation, education, and secondary stroke prevention to participants. Use of a computer-based interface offers many opportunities to monitor and improve the health of patients after stroke.

Validity of Robot-Based Assessments of Upper Extremity Function.

OBJECTIVE: To examine the validity of 5 robot-based assessments of arm motor function poststroke. DESIGN: Cross-sectional study. SETTING: Outpatient clinical research center. PARTICIPANTS: Volunteer sample of participants (N=40; age, >18y; 3-6mo poststroke) with arm motor deficits that had reached a stable plateau. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical standards included the arm motor domain of the Fugl-Meyer Assessment (FMA) and 5 secondary motor outcomes: hand/wrist subsection of the arm motor domain of the FMA, Action Research Arm Test, Box and Block test (BBT), hand motor subscale of the Stroke Impact Scale Version 2.0, and Barthel Index. Robot-based assessments included wrist targeting, finger targeting, finger movement speed, reaction time, and a robotic version of the BBT. Anatomical measures included percent injury to the corticospinal tract (CST) and extent of injury of the hand region of the primary motor cortex obtained from magnetic resonance imaging. RESULTS: Participants had moderate to severe impairment (arm motor domain of the FMA scores, 35.6±14.4; range, 13.5-60). Performance on the robot-based tests, including speed (r=.82; P<.0001), wrist targeting (r=.72; P<.0001), and finger targeting (r=.67; P<.0001), correlated significantly with the arm motor domain of the FMA scores. Wrist targeting (r=.57-.82) and finger targeting (r=.49-.68) correlated significantly with all 5 secondary motor outcomes and with percent CST injury. The robotic version of the BBT correlated significantly with the clinical BBT but was less prone to floor effects. Robot-based assessments were comparable to the arm motor domain of the FMA score in relation to percent CST injury and superior in relation to extent of injury to the hand region of the primary motor cortex. CONCLUSIONS: The present findings support using a battery of robot-based methods for assessing the upper extremity motor function in participants with chronic stroke.

Role of corpus callosum integrity in arm function differs based on motor severity after stroke.

While the corpus callosum (CC) is important to normal sensorimotor function, its role in motor function after stroke is less well understood. This study examined the relationship between structural integrity of the motor and sensory sections of the CC, as reflected by fractional anisotropy (FA), and motor function in individuals with a range of motor impairment level due to stroke. Fifty-five individuals with chronic stroke (Fugl-Meyer motor score range 14 to 61) and 18 healthy controls underwent diffusion tensor imaging and a set of motor behavior tests. Mean FA from the motor and sensory regions of the CC and from corticospinal tract (CST) were extracted and relationships with behavioral measures evaluated. Across all participants, FA in both CC regions was significantly decreased after stroke (p < 0.001) and showed a significant, positive correlation with level of motor function. However, these relationships varied based on degree of motor impairment: in individuals with relatively less motor impairment (Fugl-Meyer motor score > 39), motor status correlated with FA in the CC but not the CST, while in individuals with relatively greater motor impairment (Fugl-Meyer motor score ≤ 39), motor status correlated with FA in the CST but not the CC. The role interhemispheric motor connections play in motor function after stroke may differ based on level of motor impairment. These findings emphasize the heterogeneity of stroke, and suggest that biomarkers and treatment approaches targeting separate subgroups may be warranted.

Choice of Human-Computer Interaction Mode in Stroke Rehabilitation.

BACKGROUND AND OBJECTIVE: Advances in technology are providing new forms of human-computer interaction. The current study examined one form of human-computer interaction, augmented reality (AR), whereby subjects train in the real-world workspace with virtual objects projected by the computer. Motor performances were compared with those obtained while subjects used a traditional human-computer interaction, that is, a personal computer (PC) with a mouse. METHODS: Patients used goal-directed arm movements to play AR and PC versions of the Fruit Ninja video game. The 2 versions required the same arm movements to control the game but had different cognitive demands. With AR, the game was projected onto the desktop, where subjects viewed the game plus their arm movements simultaneously, in the same visual coordinate space. In the PC version, subjects used the same arm movements but viewed the game by looking up at a computer monitor. RESULTS: Among 18 patients with chronic hemiparesis after stroke, the AR game was associated with 21% higher game scores (P = .0001), 19% faster reaching times (P = .0001), and 15% less movement variability (P = .0068), as compared to the PC game. Correlations between game score and arm motor status were stronger with the AR version. CONCLUSIONS: Motor performances during the AR game were superior to those during the PC game. This result is due in part to the greater cognitive demands imposed by the PC game, a feature problematic for some patients but clinically useful for others. Mode of human-computer interface influences rehabilitation therapy demands and can be individualized for patients.

Connectivity measures are robust biomarkers of cortical function and plasticity after stroke.

Valid biomarkers of motor system function after stroke could improve clinical decision-making. Electroencephalography-based measures are safe, inexpensive, and accessible in complex medical settings and so are attractive candidates. This study examined specific electroencephalography cortical connectivity measures as biomarkers by assessing their relationship with motor deficits across 28 days of intensive therapy. Resting-state connectivity measures were acquired four times using dense array (256 leads) electroencephalography in 12 hemiparetic patients (7.3 ± 4.0 months post-stroke, age 26-75 years, six male/six female) across 28 days of intensive therapy targeting arm motor deficits. Structural magnetic resonance imaging measured corticospinal tract injury and infarct volume. At baseline, connectivity with leads overlying ipsilesional primary motor cortex (M1) was a robust and specific marker of motor status, accounting for 78% of variance in impairment; ipsilesional M1 connectivity with leads overlying ipsilesional frontal-premotor (PM) regions accounted for most of this (R(2) = 0.51) and remained significant after controlling for injury. Baseline impairment also correlated with corticospinal tract injury (R(2) = 0.52), though not infarct volume. A model that combined a functional measure of connectivity with a structural measure of injury (corticospinal tract injury) performed better than either measure alone (R(2) = 0.93). Across the 28 days of therapy, change in connectivity with ipsilesional M1 was a good biomarker of motor gains (R(2) = 0.61). Ipsilesional M1-PM connectivity increased in parallel with motor gains, with greater gains associated with larger increases in ipsilesional M1-PM connectivity (R(2) = 0.34); greater gains were also associated with larger decreases in M1-parietal connectivity (R(2) = 0.36). In sum, electroencephalography measures of motor cortical connectivity-particularly between ipsilesional M1 and ipsilesional premotor-are strongly related to motor deficits and their improvement with therapy after stroke and so may be useful biomarkers of cortical function and plasticity. Such measures might provide a biological approach to distinguishing patient subgroups after stroke.

Neural function, injury, and stroke subtype predict treatment gains after stroke.

OBJECTIVE: This study was undertaken to better understand the high variability in response seen when treating human subjects with restorative therapies poststroke. Preclinical studies suggest that neural function, neural injury, and clinical status each influence treatment gains; therefore, the current study hypothesized that a multivariate approach incorporating these 3 measures would have the greatest predictive value. METHODS: Patients 3 to 6 months poststroke underwent a battery of assessments before receiving 3 weeks of standardized upper extremity robotic therapy. Candidate predictors included measures of brain injury (including to gray and white matter), neural function (cortical function and cortical connectivity), and clinical status (demographics/medical history, cognitive/mood, and impairment). RESULTS: Among all 29 patients, predictors of treatment gains identified measures of brain injury (smaller corticospinal tract [CST] injury), cortical function (greater ipsilesional motor cortex [M1] activation), and cortical connectivity (greater interhemispheric M1-M1 connectivity). Multivariate modeling found that best prediction was achieved using both CST injury and M1-M1 connectivity (r(2) = 0.44, p = 0.002), a result confirmed using Lasso regression. A threshold was defined whereby no subject with >63% CST injury achieved clinically significant gains. Results differed according to stroke subtype; gains in patients with lacunar stroke were best predicted by a measure of intrahemispheric connectivity. INTERPRETATION: Response to a restorative therapy after stroke is best predicted by a model that includes measures of both neural injury and function. Neuroimaging measures were the best predictors and may have an ascendant role in clinical decision making for poststroke rehabilitation, which remains largely reliant on behavioral assessments. Results differed across stroke subtypes, suggesting the utility of lesion-specific strategies.

Motor imagery during movement activates the brain more than movement alone after stroke: a pilot study.

OBJECTIVE: To examine the neural correlates of motor imagery performed in conjunction with movement of the paretic arm after stroke. DESIGN: Cross-sectional, cohort study. SUBJECTS: Seven individuals in the chronic phase of stroke recovery (median (range): age: 58 years (37-73); time post-stroke: 9 months (4-42); upper extremity Fugl-Meyer motor score: 48 (36-64)). METHODS: Participants actively moved the paretic/right arm under two conditions while undergoing functional magnetic resonance imaging. In the motor condition, pronation/supination movements were made in response to a visual cue. In the motor + imagery condition, the same movements were performed in response to a visual cue but the participants were instructed to imagine opening and closing a doorknob during performance of the movement. RESULTS: For the motor condition, the anticipated motor network was activated and included left sensorimotor cortex and right cerebellum. For performance of the same movements during the motor + imagery condition, additional brain regions were significantly engaged including the left inferior parietal lobule and right dorsolateral prefrontal cortex. CONCLUSIONS: The addition of motor imagery to movement may provide a practical, accessible way to modulate activity in both the planning and execution components of the motor network after stroke.

A multimodal approach to understanding motor impairment and disability after stroke.

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics.

Comparing "pick and place" task in spatial Augmented Reality versus non-immersive Virtual Reality for rehabilitation setting.

Introducing computer games to the rehabilitation market led to development of numerous Virtual Reality (VR) training applications. Although VR has provided tremendous benefit to the patients and caregivers, it has inherent limitations, some of which might be solved by replacing it with Augmented Reality (AR). The task of pick-and-place, which is part of many activities of daily living (ADL's), is one of the major affected functions stroke patients mainly expect to recover. We developed an exercise consisting of moving an object between various points, following a flash light that indicates the next target. The results show superior performance of subjects in spatial AR versus non-immersive VR setting. This could be due to the extraneous hand-eye coordination which exists in VR whereas it is eliminated in spatial AR.

Targeted engagement of a dorsal premotor circuit in the treatment of post-stroke paresis.

BACKGROUND: Good motor outcome after stroke has been found to correlate with increased activity in a dorsal premotor (PMd) brain circuit, suggesting that therapeutic strategies targeting this circuit might have a favorable, causal influence on motor status. OBJECTIVE: This study addressed the hypothesis that a Premotor Therapy that exercises normal PMd functions would provide greater behavioral gains than would standard Motor Therapy; and that Premotor Therapy benefits would be greatest in patients with greater preservation of PMd circuit elements. METHODS: Patients with chronic hemiparetic stroke (n = 15) were randomized to 2-weeks of Premotor Therapy or Motor Therapy, implemented through a robotic device. RESULTS: Overall, gains were modest but significant (change in FM score, 2.1 ± 2.8 points, p < 0.02) and did not differ by treatment assignment. However, a difference between Therapies was apparent when injury to the PMd circuit was considered, as the interaction between treatment assignment and degree of corticospinal tract injury was significantly related to the change in FM score (p = 0.018): the more the corticospinal tract was spared, the greater the gains provided by Premotor Therapy. Similar results were obtained when looking at the interaction between treatment assignment and PMd function (p = 0.03). CONCLUSIONS: Targeted engagement of a brain circuit is a feasible strategy for stroke rehabilitation. This approach has maximum impact when there is less stroke injury to key elements of the targeted circuit.

A standardized approach to the Fugl-Meyer assessment and its implications for clinical trials.

BACKGROUND: Standardizing scoring reduces variability and increases accuracy. A detailed scoring and training method for the Fugl-Meyer motor assessment (FMA) is described and assessed, and implications for clinical trials considered. METHODS: A standardized FMA scoring approach and training materials were assembled, including a manual, scoring sheets, and instructional video plus patient videos. Performance of this approach was evaluated for the upper extremity portion. RESULTS: Inter- and intrarater reliability in 31 patients were excellent (intraclass correlation coefficient = 0.98-0.99), validity was excellent (r = 0.74-0.93, P < .0001), and minimal detectable change was low (3.2 points). Training required 1.5 hours and significantly reduced error and variance among 50 students, with arm FMA scores deviating from the answer key by 3.8 ± 6.2 points pretraining versus 0.9 ± 4.9 points posttraining. The current approach was implemented without incident into training for a phase II trial. Among 66 patients treated with robotic therapy, change in FMA was smaller (P ≤ .01) at the high and low ends of baseline FMA scores. CONCLUSIONS: Training with the current method improved accuracy, and reduced variance, of FMA scoring; the 20% FMA variance reduction with training would decrease sample size requirements from 137 to 88 in a theoretical trial aiming to detect a 7-point FMA difference. Minimal detectable change was much smaller than FMA minimal clinically important difference. The variation in FMA gains in relation to baseline FMA suggests that future trials consider a sliding outcome approach when FMA is an outcome measure. The current training approach may be useful for assessing motor outcomes in restorative stroke trials.