The influence of scaffolding on intrinsic motivation and autonomous adherence to a game-based, unsupervised home rehabilitation program for people with upper extremity hemiparesis due to stroke. A randomized controlled trial.

Background: This parallel, randomized controlled trial examines intrinsic motivation, adherence and motor function improvement demonstrated by two groups of subjects that performed a twelve-week, home-based upper extremity rehabilitation program. Seventeen subjects played games presenting eight to twelve discrete levels of increasing difficulty. Sixteen subjects performed the same activities controlled by success algorithms that modify game difficulty incrementally. Methods: 33 persons 20 to 80 years of age, at least six months post stroke with moderate to mild hemiparesis were randomized using a random number generator into the two groups. They were tested using the Action Research Arm Test, Upper Extremity Fugl Meyer Assessment, Stroke Impact Scale and Intrinsic Motivation Inventory pre and post training. Adherence was measured using timestamps generated by the system. Subjects had the Home Virtual Rehabilitation System [1]systems placed in their homes and were taught to perform rehabilitation games using it. Subjects were instructed to train twenty minutes per day but were allowed to train as much as they chose. Subjects trained for twelve weeks without appointments and received intermittent support from study staff. Group outcomes were compared using ANOVA. Correlations between subject demographics and adherence, as well as motor outcome, were evaluated using Pearson Correlation Coefficients. Classification and Regression Tree (CART) models were generated to predict responders using demographics and baseline measures. Results: There were 5 dropouts and no adverse events. The main effect of time was statistically significant for four of the five clinical outcome measures. There were no significant training group by time interactions. Measures of adherence did not differ between groups. 21 subjects from both groups, demonstrated clinically important improvements in UEFMA score of at least 4.25 points. Subjects with pre training UEFMA scores below 53.5 averaged a seven-point UEFMA increase. IMI scores were stable pre to post training. Conclusions: Scaffolding did not have a meaningful impact on adherence or motor function improvement. A sparsely supervised program of game-based treatment in the home was sufficient to elicit meaningful improvements in motor function and activities of daily living. Common factors considered barriers to the utilization of telerehabilitation did not impact adherence or motor outcome. Trial registration: Clinical Trials.gov - NCT03985761, Registered June 14, 2019.

A Convergent Mixed Methods Design to Assess the Use of the Home Virtual Rehabilitation System By Persons with Chronic Stroke.

Purpose: Patients poststroke utilized the Home Virtual Rehabilitation System (HoVRS) to perform home-based, gamified upper extremity rehabilitation over 12 weeks. Outcomes related to adherence and clinical improvement were collected, and semistructured interviews were conducted to assess intrinsic and extrinsic motivators that impacted engagement with the system. Methods: Subjects performed between 299 and 2020 minutes of self-scheduled, sparsely supervised hand rehabilitation activities in their homes. Results: As a group, the subjects demonstrated statistically significant improvements at the structure/function, activity, and activities of daily living levels of function. Qualitative analysis generated seven themes that both positively and negatively influenced each subject's experience with HoVRS, including challenge as a primary intrinsic motivator and pursuing additional therapy and/or a return to higher functional status as a key extrinsic motivator. Subjects' ratings of the system using the Intrinsic Motivation Inventory before and after treatment were uniformly positive, but interview-based feedback was more balanced between positive and negative.

A Review of the Use of Gaze and Pupil Metrics to Assess Mental Workload in Gamified and Simulated Sensorimotor Tasks.

Gaze and pupil metrics are used to represent higher cognitive processes in a variety of contexts. One growing area of research is the real-time assessment of workload and corresponding effort in gamified or simulated cognitive and motor tasks, which will be reviewed in this paper. While some measurements are consistent across studies, others vary and are likely dependent on the nature of the effort required by the task and the resulting changes in arousal. Pupil diameter is shown to consistently increase with task effort and arousal; however, the valence of arousal must be considered. In many cases, measures of pupil diameter were sensitive to both excessive and insufficient challenge. Overall, it is evident that gaze and pupil metrics are valuable to assess the cognitive state during gamified and simulated tasks, and further research is indicated regarding their use in clinical populations in rehabilitation to inform optimally engaging interventions.

Robust walking control of a lower limb rehabilitation exoskeleton coupled with a musculoskeletal model via deep reinforcement learning.

BACKGROUND: Few studies have systematically investigated robust controllers for lower limb rehabilitation exoskeletons (LLREs) that can safely and effectively assist users with a variety of neuromuscular disorders to walk with full autonomy. One of the key challenges for developing such a robust controller is to handle different degrees of uncertain human-exoskeleton interaction forces from the patients. Consequently, conventional walking controllers either are patient-condition specific or involve tuning of many control parameters, which could behave unreliably and even fail to maintain balance. METHODS: We present a novel, deep neural network, reinforcement learning-based robust controller for a LLRE based on a decoupled offline human-exoskeleton simulation training with three independent networks, which aims to provide reliable walking assistance against various and uncertain human-exoskeleton interaction forces. The exoskeleton controller is driven by a neural network control policy that acts on a stream of the LLRE's proprioceptive signals, including joint kinematic states, and subsequently predicts real-time position control targets for the actuated joints. To handle uncertain human interaction forces, the control policy is trained intentionally with an integrated human musculoskeletal model and realistic human-exoskeleton interaction forces. Two other neural networks are connected with the control policy network to predict the interaction forces and muscle coordination. To further increase the robustness of the control policy to different human conditions, we employ domain randomization during training that includes not only randomization of exoskeleton dynamics properties but, more importantly, randomization of human muscle strength to simulate the variability of the patient's disability. Through this decoupled deep reinforcement learning framework, the trained controller of LLREs is able to provide reliable walking assistance to patients with different degrees of neuromuscular disorders without any control parameter tuning. RESULTS AND CONCLUSION: A universal, RL-based walking controller is trained and virtually tested on a LLRE system to verify its effectiveness and robustness in assisting users with different disabilities such as passive muscles (quadriplegic), muscle weakness, or hemiplegic conditions without any control parameter tuning. Analysis of the RMSE for joint tracking, CoP-based stability, and gait symmetry shows the effectiveness of the controller. An ablation study also demonstrates the strong robustness of the control policy under large exoskeleton dynamic property ranges and various human-exoskeleton interaction forces. The decoupled network structure allows us to isolate the LLRE control policy network for testing and sim-to-real transfer since it uses only proprioception information of the LLRE (joint sensory state) as the input. Furthermore, the controller is shown to be able to handle different patient conditions without the need for patient-specific control parameter tuning.

Laboratory-Based Examination of the Reliability and Validity of Kinematic Measures of Wrist and Finger Function Collected by a Telerehabilitation System in Persons with Chronic Stroke.

We have developed the New Jersey Institute of Technology-Home Virtual Rehabilitation System (NJIT-HoVRS) to facilitate intensive, hand-focused rehabilitation in the home. We developed testing simulations with the goal of providing richer information for clinicians performing remote assessments. This paper presents the results of reliability testing examining differences between in-person and remote testing as well as discriminatory and convergent validity testing of a battery of six kinematic measures collected with NJIT-HoVRS. Two different groups of persons with upper extremity impairments due to chronic stroke participated in two separate experiments. Data Collection: All data collection sessions included six kinematic tests collected with the Leap Motion Controller. Measurements collected include hand opening range, wrist extension range, pronation-supination range, hand opening accuracy, wrist extension accuracy, and pronation-supination accuracy. The system usability was evaluated by therapists performing the reliability study using the System Usability Scale. When comparing the in-laboratory collection and the first remote collection, the intra-class correlation coefficients (ICC) for three of the six measurements were above 0.900 and the other three were between 0.500 and 0.900. Two of the first remote collection/second remote collection ICCs were above 0.900, and the other four were between 0.600 and 0.900. The 95% confidence intervals for these ICC were broad, suggesting that these preliminary analyses need to be confirmed by studies with larger samples. The therapist's SUS scores ranged from 70 to 90. The mean was 83.1 (SD = 6.4), which is consistent with industry adoption. There were statistically significant differences in the kinematic scores when comparing unimpaired and impaired UE for all six measures. Five of six impaired hand kinematic scores and five of six impaired/unimpaired hand difference scores demonstrated correlations between 0.400 and 0.700 with UEFMA scores. Reliability for all measures was acceptable for clinical practice. Discriminant and convergent validity testing suggest that scores on these tests may be meaningful and valid. Further testing in a remote setting is necessary to validate this process.

EEG Based Resting State Connectivity Changes in the Motor Cortex Associated with Upper Limb Motor Recovery in the Subacute Period Post-Stroke.

Stroke is a heterogeneous condition that would benefit from valid biomarkers of recovery for research and in the clinic. We evaluated the change in resting state connectivity (RSC) via electroencephalography (EEG) in motor areas, as well as motor recovery of the affected upper limb, in the subacute phase post-stroke. Fifteen participants who had sustained a subcortical stroke were included in this study. The group made significant gains in upper limb impairment as measured by the Upper Extremity Fugl-Meyer Assessment (UEFMA) from baseline to four months post-stroke (24.78 (SD 5.4)). During this time, there was a significant increase in RSC in the beta band from contralesional M1 to ipsilesional M1. We propose that this change in RSC may have contributed to the motor recovery seen in this group. Clinical Relevance- This study evaluates resting state connectivity measured via EEG as a neural biomarker of recovery post-stroke. Biomarkers can help clinicians understand the potential for recovery after stroke and thus help them to establish therapy goals and determine treatment plans.

Evaluation of Changes in Kinematic Measures of Three Dimensional Reach to Grasp Movements in the Early Subacute Period of Recovery from Stroke.

This study examines longitudinal data of subjects initially examined in the early subacute period of recovery following a stroke with a test of reach to grasp (RTG) kinematics in an attempt to identify changes in movement patterns during the period of heightened neural recovery following a stroke. Subjects (n=8) were a convenience sample of persons with stroke that participated in an intervention trial. Baseline Upper Extremity Fugl Meyer Assessment (UEFMA) scores ranged between 31 and 52 and ages were between 49 and 83. The UEFMA and RTG test were collected prior to intervention, immediately after the intervention (approximately 18 days later post baseline) and one month after the intervention. RTG data for the uninvolved UE was collected at the one-month session. Subjects reached for objects placed on a table 10 cm from their sternums, picking them up and placing them on a target 30 cm from their acromioclavicular joints. Data was collected using an optical motion capture system. Active makers were placed on each fingertip, metacarpophalangeal, and proximal interphalangeal joint. Four additional passive markers were placed on the dorsum of the hand, the elbow, the shoulder, and the sternum. Subjects demonstrated statistically significant improvements in reaching duration, reaching trajectory smoothness, time after peak velocity and peak grip aperture. All of these measures correlated significantly with improvements in UEFMA. Clinical Relevance- Kinematic measures of reaching and grasping collected early in the subacute period of recovery from stroke may offer insight into specific aspects of the recovery of upper extremity motor function that differ from the information gleaned from clinical scales.

Reinforcement Learning and Control of a Lower Extremity Exoskeleton for Squat Assistance.

A significant challenge for the control of a robotic lower extremity rehabilitation exoskeleton is to ensure stability and robustness during programmed tasks or motions, which is crucial for the safety of the mobility-impaired user. Due to various levels of the user's disability, the human-exoskeleton interaction forces and external perturbations are unpredictable and could vary substantially and cause conventional motion controllers to behave unreliably or the robot to fall down. In this work, we propose a new, reinforcement learning-based, motion controller for a lower extremity rehabilitation exoskeleton, aiming to perform collaborative squatting exercises with efficiency, stability, and strong robustness. Unlike most existing rehabilitation exoskeletons, our exoskeleton has ankle actuation on both sagittal and front planes and is equipped with multiple foot force sensors to estimate center of pressure (CoP), an important indicator of system balance. This proposed motion controller takes advantage of the CoP information by incorporating it in the state input of the control policy network and adding it to the reward during the learning to maintain a well balanced system state during motions. In addition, we use dynamics randomization and adversary force perturbations including large human interaction forces during the training to further improve control robustness. To evaluate the effectiveness of the learning controller, we conduct numerical experiments with different settings to demonstrate its remarkable ability on controlling the exoskeleton to repetitively perform well balanced and robust squatting motions under strong perturbations and realistic human interaction forces.

Virtual Rehabilitation of the Paretic Hand and Arm in Persons With Stroke: Translation From Laboratory to Rehabilitation Centers and the Patient's Home.

The anatomical and physiological heterogeneity of strokes and persons with stroke, along with the complexity of normal upper extremity movement make the possibility that any single treatment approach will become the definitive solution for all persons with upper extremity hemiparesis due to stroke unlikely. This situation and the non-inferiority level outcomes identified by many studies of virtual rehabilitation are considered by some to indicate that it is time to consider other treatment modalities. Our group, among others, has endeavored to build on the initial positive outcomes in studies of virtual rehabilitation by identifying patient populations, treatment settings and training schedules that will best leverage virtual rehabilitation's strengths. We feel that data generated by our lab and others suggest that (1) persons with stroke may adapt to virtual rehabilitation of hand function differently based on their level of impairment and stage of recovery and (2) that less expensive, more accessible home based equipment seems to be an effective alternative to clinic based treatment that justifies continued optimism and study.

Hand Focused Upper Extremity Rehabilitation in the Subacute Phase Post-stroke Using Interactive Virtual Environments.

Introduction: Innovative motor therapies have attempted to reduce upper extremity impairment after stroke but have not made substantial improvement as over 50% of people post-stroke continue to have sensorimotor deficits affecting their self-care and participation in daily activities. Intervention studies have focused on the role of increased dosing, however recent studies have indicated that timing of rehabilitation interventions may be as important as dosing and importantly, that dosing and timing interact in mediating effectiveness. This study is designed to empirically test dosing and timing. Methods and Analysis: In this single-blinded, interventional study, subjects will be stratified on two dimensions, impairment level (Fugl-Meyer Upper Extremity Assessment (FM) and presence or absence of Motor Evoked Potentials (MEPs) as follows; (1) Severe, FM score 10-19, MEP+, (2) Severe, FM score 10-19, MEP-, (3) Moderate, FM score 20-49, MEP+, (4) Moderate, FM score 20-49, MEP-. Subjects not eligible for TMS will be assigned to either group 2 (if severe) or group 3 (if moderate). Stratified block randomization will then be used to achieve a balanced assignment. Early Robotic/VR Therapy (EVR) experimental group will receive in-patient usual care therapy plus an extra 10 h of intensive upper extremity therapy focusing on the hand using robotically facilitated rehabilitation interventions presented in virtual environments and initiated 5-30 days post-stroke. Delayed Robotic/VR Therapy (DVR) experimental group will receive the same intervention but initiated 30-60 days post-stroke. Dose-matched usual care group (DMUC) will receive an extra 10 h of usual care initiated 5-30 days post-stroke. Usual Care Group (UC) will receive the usual amount of physical/occupational therapy. Outcomes: There are clinical, neurophysiological, and kinematic/kinetic measures, plus measures of daily arm use and quality of life. Primary outcome is the Action Research Arm Test (ARAT) measured at 4 months post-stroke. Discussion: Outcome measures will be assessed to determine whether there is an early time period in which rehabilitation will be most effective, and whether there is a difference in the recapture of premorbid patterns of movement vs. the development of an efficient, but compensatory movement strategy. Ethical Considerations: The IRBs of New Jersey Institute of Technology, Rutgers University, Northeastern University, and Kessler Foundation reviewed and approved all study protocols. Study was registered in https://ClinicalTrials.gov (NCT03569059) prior to recruitment. Dissemination will include submission to peer-reviewed journals and professional presentations.

Development of the Home based Virtual Rehabilitation System (HoVRS) to remotely deliver an intense and customized upper extremity training.

BACKGROUND: After stroke, sustained hand rehabilitation training is required for continuous improvement and maintenance of distal function. METHODS: In this paper, we present a system designed and implemented in our lab: the Home based Virtual Rehabilitation System (HoVRS). Fifteen subjects with chronic stroke were recruited to test the feasibility of the system as well as to refine the design and training protocol to prepare for a future efficacy study. HoVRS was placed in subjects' homes, and subjects were asked to use the system at least 15 min every weekday for 3 months (12 weeks) with limited technical support and remote clinical monitoring. RESULTS: All subjects completed the study without any adverse events. Subjects on average spent 13.5 h using the system. Clinical and kinematic data were collected pre and post study in the subject's home. Subjects demonstrated a mean increase of 5.2 (SEM = 0.69) on the Upper Extremity Fugl-Meyer Assessment (UEFMA). They also demonstrated improvements in six measurements of hand kinematics. In addition, a combination of these kinematic measures was able to predict a substantial portion of the variability in the subjects' UEFMA score. CONCLUSION: Persons with chronic stroke were able to use the system safely and productively with minimal supervision resulting in measurable improvements in upper extremity function.

Autonomous Use of the Home Virtual Rehabilitation System: A Feasibility and Pilot Study.

Objective: This article describes the findings of a study examining the ability of persons with strokes to use home virtual rehabilitation system (HoVRS), a home-based rehabilitation system, and the impact of motivational enhancement techniques on subjects' motivation, adherence, and motor function improvements subsequent to a 3-month training program. Materials and Methods: HoVRS integrates a Leap Motion controller, a passive arm support, and a suite of custom-designed hand rehabilitation simulations. For this study, we developed a library of three simulations, which include activities such as flexing and extending fingers to move a car, flying a plane with wrist movement, and controlling an avatar running in a maze using reaching movements. Two groups of subjects, the enhanced motivation (EM) group and the unenhanced control (UC) group, used the system for 12 weeks in their homes. The EM group trained using three simulations that provided 8-12 levels of difficulty and complexity. Graphics and scoring opportunities increased at each new level. The UC group performed the same simulations, but difficulty was increased utilizing an algorithm that increased difficulty incrementally, making adjustments imperceptible. Results: Adherence to both the EM and UC protocols exceeded adherence to home exercise programs described in the stroke rehabilitation literature. Both groups demonstrated improvements in upper extremity function. Intrinsic motivation levels were better for the EM group and motivation levels were maintained for the 12-week protocol. Conclusion: A 12-week home-based training program using HoVRS was feasible. Motivational enhancement may have a positive impact on motivation, adherence, and motor outcome.

Intensive virtual reality and robotic based upper limb training compared to usual care, and associated cortical reorganization, in the acute and early sub-acute periods post-stroke: a feasibility study.

BACKGROUND: There is conflict regarding the benefits of greater amounts of intensive upper limb rehabilitation in the early period post-stroke. This study was conducted to test the feasibility of providing intensive therapy during the early period post-stroke and to develop a randomized control trial that is currently in process. Specifically, the study investigated whether an additional 8 h of specialized, intensive (200-300 separate hand or arm movements per hour) virtual reality (VR)/robotic based upper limb training introduced within 1-month post-stroke resulted in greater improvement in impairment and behavior, and distinct changes in cortical reorganization measured via Transcranial Magnetic Stimulation (TMS), compared to that of a control group. METHODS: Seven subjects received 8-1 h sessions of upper limb VR/robotic training in addition to their inpatient therapy (PT, OT, ST). Six subjects only received their inpatient therapy. All were tested on measures of impairment [Upper Extremity Fugl-Meyer Assessment (UEFMA), Wrist AROM, Maximum Pinch Force], behavior [Wolf Motor Function Test (WMFT)], and also received TMS mapping until 6 months post training. ANOVAs were conducted to measure differences between groups across time for all outcome measures. Associations between changes in ipsilesional cortical maps during the early period of enhanced neuroplasticity and long-term changes in upper limb impairment and behavior measures were evaluated. RESULTS: The VR/robotic group made significantly greater improvements on UEFMA and Wrist AROM scores compared to the usual care group. There was also less variability in the association between changes in the First Dorsal Interosseus (FDI) muscle map area and WMFT and Maximum Force change scores for the VR/robotic group. CONCLUSIONS: An additional 8 h of intensive VR/robotic based upper limb training initiated within the first month post-stroke may promote greater gains in impairment compared to usual care alone. Importantly, the data presented demonstrated the feasibility of conducting this intervention and multiple outcome measures (impairment, behavioral, neurophysiological) in the early period post-stroke.

Coordination of reach-to-grasp in physical and haptic-free virtual environments.

BACKGROUND: Virtual reality (VR) offers unprecedented opportunity as a scientific tool to study visuomotor interactions, training, and rehabilitation applications. However, it remains unclear if haptic-free hand-object interactions in a virtual environment (VE) may differ from those performed in the physical environment (PE). We therefore sought to establish if the coordination structure between the transport and grasp components remain similar whether a reach-to-grasp movement is performed in PE and VE. METHOD: Reach-to-grasp kinematics were examined in 13 healthy right-handed young adults. Subjects were instructed to reach-to-grasp-to-lift three differently sized rectangular objects located at three different distances from the starting position. Object size and location were matched between the two environments. Contact with the virtual objects was based on a custom collision detection algorithm. Differences between the environments were evaluated by comparing movement kinematics of the transport and grasp components. RESULTS: Correlation coefficients, and the slope of the regression lines, between the reach and grasp components were similar for the two environments. Likewise, the kinematic profiles of the transport velocity and grasp aperture were strongly correlated across the two environments. A rmANOVA further identified some similarities and differences in the movement kinematics between the two environments - most prominently that the closure phase of reach-to-grasp movement was prolonged when movements were performed in VE. CONCLUSIONS: Reach-to-grasp movement patterns performed in a VE showed both similarities and specific differences compared to those performed in PE. Additionally, we demonstrate a novel approach for parsing the reach-to-grasp movement into three phases- initiation, shaping, closure- based on established kinematic variables, and demonstrate that the differences in performance between the environments are attributed to the closure phase. We discuss this in the context of how collision detection parameters may modify hand-object interactions in VE. Our study shows that haptic-free VE may be a useful platform to study reach-to-grasp movements, with potential implications for haptic-free VR in neurorehabilitation.

The Association Between Reorganization of Bilateral M1 Topography and Function in Response to Early Intensive Hand Focused Upper Limb Rehabilitation Following Stroke Is Dependent on Ipsilesional Corticospinal Tract Integrity.

Transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs) are an established proxy of corticospinal excitability. As a binary measure, the presence (MEP+) or absence (MEP-) of ipsilesional hemisphere MEPs early following stroke is a robust indicator of long-term recovery, however this measure does not provide information about spatial cortical reorganization. MEPs have been systematically acquired over the sensorimotor cortex to "map" motor topography. In this investigation we compared the degree to which functional improvements resulting from early (<3 months post-stroke) intensive hand focused upper limb rehabilitation correlate with changes in motor topography between MEP+ and MEP- individuals. Following informed consent, 17 individuals (4 Female, 60.3 ± 9.4 years, 24.6 ± 24.01 days post first time stroke) received 8 one hour-sessions of training with virtual reality (VR)/Robotic simulations. Clinical tests [Box and Blocks Test (BBT), Wolf Motor Function Test (WMFT), Upper Extremity Fugl-Meyer (UEFMA)], kinematic and kinetic assessments [finger Active Range of Motion (finger AROM), Maximum Pinch Force (MPF)], and bilateral TMS mapping of 5 hand muscles were performed prior to (PRE), directly following (POST), and 1 month following (1M) training. Participants were divided into two groups (MEP+, MEP-) based on whether an MEP was present in the affected first dorsal interosseous (FDI) at any time point. MEP+ individuals improved significantly more than MEP- individuals from PRE to 1M on the WMFT, BBT, and finger AROM scores. Ipsilesional hemisphere FDI area increased significantly with time in the MEP+ group. FDI area of the contralesional hemisphere was not significantly different across time points or groups. In the MEP+ group, significant correlations were observed between PRE-1M changes in ipsilesional FDI area and WMFT, BBT, and finger AROM, and contralesional FDI area and UEFMA and MPF. In the MEP- group, no significant correlations were found between changes in contralesional FDI area and functional outcomes. We report preliminary evidence in a small sample that patterns of recovery and the association of recovery to bilateral changes in motor topography may depend on integrity of the ipsilesional cortical spinal tract as assessed by the presence of TMS evoked MEPs.

EEG Based Analysis of Cortical Activity during Mirror Visual Feedback Target-Directed Movement.

In mirror visual feedback (MVF) based rehabilitation, the illusion of mirror reflection of volitional movement of non-paretic limb tends to have a modulatory effect on visuomotor and sensorimotor brain activations. This paper presents EEG based analysis of hemispheric activation asymmetry within the beta band (15-28 Hz) when MVF is combined with a target-directed hand motor task in a block design versus a similar task without any target requirements. MVF coupled with target-directed movement was associated with a decrease in hemispheric asymmetry in both preparation and execution phases of movement. These results emphasize the potential importance of incorporating visuomotor goals into the task to maximize the rehabilitation outcomes of MVF-based training activities.

The Effect of Movement Phase on the Contralaterally Coordinated Paired Associative Stimulation-Induced Excitability.

Paired associative stimulation (PAS) has been shown to increase corticospinal excitability (CSE) providing a promising adjuvant therapeutic approach for stroke. Combining PAS with movement of the stimulated limb may further increase enhancement of CSE, however, individuals with moderate to severe stroke may not be able to engage in the necessary repetitive voluntary movements of the paretic limb. The objective of this study was to investigate the feasibility of contralaterally coordinated PAS (ccPAS) applied to the resting hand extensors during fast extension of the contralateral hand. A potential dependency of CSE modulation on the phase of the movement of the opposite hand was evaluated. Eleven participants each completed three session: PAS applied to the resting right hand during the preparation phase of the extension of the contralateral (left) hand; PAS applied during the execution phase of the left hand extension; and PAS applied with both hands at rest. Motor evoked potentials (MEPs) were evoked from the right extensor digitorum communis (EDC) and flexor digitorum superficialis (FDS) muscles prior and immediately after each session. PAS delivered during the muscle contraction of the left hand and PAS delivered at rest both increased the MEP amplitude in the right EDC. PAS delivered before the left hand movement onset led to a decrease in the MEP amplitude measured in the right EDC muscle. We conclude that PAS induced bidirectional changes in the amplitude of MEPs that were dependent on the phase of the movement of the opposite hand.

Parietal Activation Associated With Target-Directed Right Hand Movement Is Lateralized by Mirror Feedback to the Ipsilateral Hemisphere.

Current research shows promise in restoring impaired hand function after stroke with the help of Mirror Visual Feedback (MVF), putatively by facilitating activation of sensorimotor areas of the brain ipsilateral to the moving limb. However, the MVF related clinical effects show variability across studies. MVF tasks that have been used place varying amounts of visuomotor demand on one's ability to complete the task. Therefore, we ask here whether varying visuomotor demand during MVF may translate to differences in brain activation patterns. If so, we argue that this may provide a mechanistic explanation for variable clinical effects. To address this, we used functional magnetic resonance imaging (fMRI) to investigate the interaction of target directed movement and MVF on the activation of, and functional connectivity between, regions within the visuomotor network. In an event-related fMRI design, twenty healthy subjects performed finger flexion movements using their dominant right hand, with feedback presented in a virtual reality (VR) environment. Visual feedback was presented in real time VR as either veridical feedback with and without a target (VT+ and VT-, respectively), or MVF with and without a target (MT+ and MT-, respectively). fMRI contrasts revealed predominantly activation in the ipsilateral intraparietal sulcus for the main effect of MVF and bilateral superior parietal activation for the main effect of target. Importantly, we noted significant and robust activation lateralized to the ipsilateral parietal cortex alone in the MT+ contrast with respect to the other conditions. This suggests that combining MVF with targeted movements performed using the right hand may redirect enhanced bilateral parietal activation due to target presentation to the ipsilateral cortex. Moreover, functional connectivity analysis revealed that the interaction between the ipsilateral parietal lobe and the motor cortex was significantly greater during target-directed movements with mirror feedback compared to veridical feedback. These findings provide a normative basis to investigate the integrity of these networks in patient populations. Identification of the brain regions involved in target directed movement with MVF in stroke may have important implications for optimal delivery of MVF based therapy.

Neural Patterns of Reorganization after Intensive Robot-Assisted Virtual Reality Therapy and Repetitive Task Practice in Patients with Chronic Stroke.

Several approaches to rehabilitation of the hand following a stroke have emerged over the last two decades. These treatments, including repetitive task practice (RTP), robotically assisted rehabilitation and virtual rehabilitation activities, produce improvements in hand function but have yet to reinstate function to pre-stroke levels-which likely depends on developing the therapies to impact cortical reorganization in a manner that favors or supports recovery. Understanding cortical reorganization that underlies the above interventions is therefore critical to inform how such therapies can be utilized and improved and is the focus of the current investigation. Specifically, we compare neural reorganization elicited in stroke patients participating in two interventions: a hybrid of robot-assisted virtual reality (RAVR) rehabilitation training and a program of RTP training. Ten chronic stroke subjects participated in eight 3-h sessions of RAVR therapy. Another group of nine stroke subjects participated in eight sessions of matched RTP therapy. Functional magnetic resonance imaging (fMRI) data were acquired during paretic hand movement, before and after training. We compared the difference between groups and sessions (before and after training) in terms of BOLD intensity, laterality index of activation in sensorimotor areas, and the effective connectivity between ipsilesional motor cortex (iMC), contralesional motor cortex, ipsilesional primary somatosensory cortex (iS1), ipsilesional ventral premotor area (iPMv), and ipsilesional supplementary motor area. Last, we analyzed the relationship between changes in fMRI data and functional improvement measured by the Jebsen Taylor Hand Function Test (JTHFT), in an attempt to identify how neurophysiological changes are related to motor improvement. Subjects in both groups demonstrated motor recovery after training, but fMRI data revealed RAVR-specific changes in neural reorganization patterns. First, BOLD signal in multiple regions of interest was reduced and re-lateralized to the ipsilesional side. Second, these changes correlated with improvement in JTHFT scores. Our findings suggest that RAVR training may lead to different neurophysiological changes when compared with traditional therapy. This effect may be attributed to the influence that augmented visual and haptic feedback during RAVR training exerts over higher-order somatosensory and visuomotor areas.

The Effects of Mirror Feedback during Target Directed Movements on Ipsilateral Corticospinal Excitability.

Mirror visual feedback (MVF) training is a promising technique to promote activation in the lesioned hemisphere following stroke, and aid recovery. However, current outcomes of MVF training are mixed, in part, due to variability in the task undertaken during MVF. The present study investigated the hypothesis that movements directed toward visual targets may enhance MVF modulation of motor cortex (M1) excitability ipsilateral to the trained hand compared to movements without visual targets. Ten healthy subjects participated in a 2 × 2 factorial design in which feedback (veridical, mirror) and presence of a visual target (target present, target absent) for a right index-finger flexion task were systematically manipulated in a virtual environment. To measure M1 excitability, transcranial magnetic stimulation (TMS) was applied to the hemisphere ipsilateral to the trained hand to elicit motor evoked potentials (MEPs) in the untrained first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles at rest prior to and following each of four 2-min blocks of 30 movements (B1-B4). Targeted movement kinematics without visual feedback was measured before and after training to assess learning and transfer. FDI MEPs were decreased in B1 and B2 when movements were made with veridical feedback and visual targets were absent. FDI MEPs were decreased in B2 and B3 when movements were made with mirror feedback and visual targets were absent. FDI MEPs were increased in B3 when movements were made with mirror feedback and visual targets were present. Significant MEP changes were not present for the uninvolved ADM, suggesting a task-specific effect. Analysis of kinematics revealed learning occurred in visual target-directed conditions, but transfer was not sensitive to mirror feedback. Results are discussed with respect to current theoretical mechanisms underlying MVF-induced changes in ipsilateral excitability.