Computational neurorehabilitation: modeling plasticity and learning to predict recovery

Despite progress in using computational approaches to inform medicine and neuroscience in the last 30 years, there have been few attempts to model the mechanisms underlying sensorimotor rehabilitation. We argue that a fundamental understanding of neurologic recovery, and as a result accurate predictions at the individual level, will be facilitated by developing computational models of the salient neural processes, including plasticity and learning systems of the brain, and integrating them into a context specific to rehabilitation. Here, we therefore discuss Computational Neurorehabilitation, a newly emerging field aimed at modeling plasticity and motor learning to understand and improve movement recovery of individuals with neurologic impairment. We first explain how the emergence of robotics and wearable sensors for rehabilitation is providing data that make development and testing of such models increasingly feasible. We then review key aspects of plasticity and motor learning that such models will incorporate. We proceed by discussing how computational neurorehabilitation models relate to the current benchmark in rehabilitation modeling – regression-based, prognostic modeling. We then critically discuss the first computational neurorehabilitation models, which have primarily focused on modeling rehabilitation of the upper extremity after stroke, and show how even simple models have produced novel ideas for future investigation. Finally, we conclude with key directions for future research, anticipating that soon we will see the emergence of mechanistic models of motor recovery that are informed by clinical imaging results and driven by the actual movement content of rehabilitation therapy as well as wearable sensor-based records of daily activity

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration

Kinematic changes following robotic-assisted upper extremity rehabilitation in children with hemiplegia : dosage effects on movement time

Indiana University-Purdue University Indianapolis (IUPUI)Background: Rehabilitation Robotics (RR) has become a more widely used and better understood treatment intervention and research tool in the last 15 years. Traditional research involves pre and post-test outcomes, making it difficult to analyze changes in behavior during the treatment process. Harnessing kinematics captured throughout each treatment allows motor learning to be quantified and questions of application and dosing to be answered. Objective: The aims of this secondary analysis were: (i) to investigate the impact of treatment presentation during RR on upper extremity movement time (mt) in children with hemiplegic cerebral palsy (CP) and (ii) to investigate the impact of training structure (dose and intensity) on mt in children with CP participating in RR. Methods: Subjects completed 16 intervention sessions of RR (2 x week; 8 weeks) with a total of 1,024 repetitions of movement per session and three assessments: pre, post and 6 month f/u. During each assessment and intervention, subjects completed “one-way record” assessments tracking performance on a planar task without robotic assistance. Kinematics from these records were extracted to assess subject performance over the course of and within sessions. Results: For all participants, a significant decrease in mt was found at post-test and follow-up. No significant differences were found in mt for age, severity or group placement. A significant interaction was found between treatment day, block and group (p = .033). Significant mt differences were found between the three blocks of intervention within individual days (p = .001). Specifically, significant differences were found over the last block of treatment (p = .032) and between successive treatment days (p = .001). Conclusion: The results indicate that for children with CP participating in RR, the number of repetitions per session is important. We hypothesized that children’s performance would plateau during a treatment day as attention waned, the opposite proved to be true. Despite the high-number of repetitions and associated cognitive demand, subjects’ performance actually trended upwards throughout the 1,024 repetitions suggesting that children were able to tolerate and learn from a high volume of repetitions

Trunk Rehabilitation Using Cable-Driven Robotic Systems

Upper body control is required to complete many daily tasks. One needs to stabilize the head and trunk over the pelvis, as one shifts the center of mass to interact with the world. While healthy individuals can perform activities that require leaning, reaching, and grasping readily, those with neurological and musculoskeletal disorders present with control deficits. These deficits can lead to difficulty in shifting the body center of mass away from the stable midline, leading to functional limitations and a decline in the quality of activity. Often these patient groups use canes, walkers, and wheelchairs for support, leading to occasional strapping or joint locking of the body for trunk stabilization. Current rehabilitation strategies focus on isolated components of stability. This includes strengthening, isometric exercises, hand-eye coordination tasks, isolated movement, and proprioceptive training. Although all these components are evidence based and directly correlate to better stability, motor learning theories such as those by Nikolai Bernstein, suggest that task and context specific training can lead to better outcomes. In specific, based on our experimentation, we believe functional postural exploration, while encompassing aspects of strengthening, hand-eye coordination, and proprioceptive feedback can provide better results. In this work, we present two novel cable robotic platforms for seated and standing posture training. The Trunk Support Trainer (TruST) is a platform for seated posture rehabilitation that provides controlled external wrench on the human trunk in any direction in real-time. The Stand Trainer is a platform for standing posture rehabilitation that can control the trunk, pelvis, and knees, simultaneously. The system works through the use of novel force-field algorithms that are modular and user-specific. The control uses an assist-as-needed strategy to apply forces on the user during regions of postural instability. The device also allows perturbations for postural reactive training. We have conducted several studies using healthy adult populations and pilot studies on patient groups including cerebral palsy, cerebellar ataxia, and spinal cord injury. We propose new training methods that incorporate motor learning theory and objective interventions for improving posture control. We identify novel methods to characterize posture in form of the “8-point star test”. This is to assess the postural workspace. We also demonstrate novel methods for functional training of posture and balance. Our results show that training with our robotic platforms can change the trunk kinematics. Specifically, healthy adults are able to translate the trunk further and rotate the trunk more anteriorly in the seated position. In the standing position, they can alter their reach strategy to maintain the upper trunk more vertically while reaching. Similarly, Cerebral Palsy patients improve their trunk translations, reaching workspace, and maintain a more vertical posture after training, in the seated position. Our results also showed that an Ataxia patient was able to improve their reaching workspace and trunk translations in the standing position. Finally, our results show that the robotic platforms can successfully reduce trunk and pelvis sway in spinal cord injury patients. The results of the pilot studies suggest that training with our robotic platforms and methods is beneficial in improving trunk control

Technology-supported training of arm-hand skills in stroke

Impaired arm-hand performance is a serious consequence of stroke that is associated with reduced self-efficacy and poor quality of life. Task-oriented arm training is a therapy approach that is known to improve skilled arm-hand performance, even in chronic stages after stroke. At the start of this project, little knowledge had been consolidated regarding taskoriented arm training characteristics, especially in the field of technology-supported rehabilitation. The feasibility and effects of technology-supported client-centred task-oriented training on skilled arm-hand performance had not been investigated but to a very limited degree. Reviewing literature on rehabilitation and motor learning in stroke led to the identification of therapy oriented criteria for rehabilitation technology aiming to influence skilled arm-hand performance (chapter 2). Most rehabilitation systems reported in literature to date are robotic systems that are aimed at providing an engaging exercise environment and feedback on motor performance. Both, feedback and engaging exercises are important for motivating patients to perform a high number of exercise repetitions and prolonged training, which are important factors for motor learning. The review also found that current rehabilitation technology is focussed mainly on providing treatment at a function level, thereby improving joint range of motion, muscle strength and parameters such as movement speed and smoothness of movement during analytical movements. However, related research has found no effects of robot-supported training at the activity level. The review concluded that a challenge exists for upper extremity rehabilitation technology in stroke patients to also provide more patienttailored task-oriented arm-hand training in natural environments to support the learning of skilled arm-hand performance. Besides mapping the strengths of different technological solutions, the use of outcome measures and training protocols needs to become more standardized across similar interventions, in order to help determine which training solutions are most suitable for specific patient categories. Chapter 4 contributes towards such a standardization of outcome measurement. A concept is introduced which may guide the clinician/researcher to choose outcome measures for evaluating specific and generalized training effects. As an initial operationalization of this concept, 28 test batteries that have been used in 16 task-oriented training interventions were rated as to whether measurement components were measured by the test. Future research is suggested that elaborates the concept with information on the relative weighing of components in each test, with more test batteries (which may lead to additional components) and by adding more test properties into the concept (e.g. psychometric properties of the tests, possible floor- or ceiling effects). Task-oriented training is one of the training approaches that has been shown to be beneficial for skilled arm-hand performance after stroke. Important mechanisms for motor learning that are identified are patient motivation for such training, and the learning of efficient goaloriented movement strategies and task-specific problem solving. In this thesis we operationalize task-oriented training in terms of 15 components (chapter 3). A systematic review that included 16 randomized controlled trials using task-oriented training in stroke patients, evaluated the effects of these training components on skilled arm-hand performance. The number of training components used in an intervention aimed at improving arm-hand performance after stroke was not associated with the post-treatment effect size. Distributed practice and feedback were associated with the largest post-intervention effect sizes. Random practice and use of clear functional training goals were associated with the largest follow-up effect sizes. It may be that training components that optimize the storage of learned motor performance in the long-term memory are associated with larger treatment effects. Unfortunately, feedback, random practice and distributed practice were reported in very few of the included randomized controlled trials (in only 6,3 and 1 out of the 17 studies respectively). Client-centred training, i.e. training on exercises that support goals that are selected by the patients themselves, improves patient motivation for training. Motivation in turn has proven to positively influence motor learning in stroke patients, as attention during training is heightened and storage of information in the long-term memory improves. Chapter 5 reports on an interview of 40 stroke patients, investigating into training preferences. A list of 46 skills, ranked according to descending training preference scores, was provided that can be used for implementation of exercises in rehabilitation technology, in order for technologysupported training to be client-centred. Chapter 6 introduces T-TOAT, a technology supported task-oriented arm training method that was developed together with colleagues at Adelante (Hoensbroek, NL). T-TOAT enables the implementation of exercises that support task-oriented training in rehabilitation technology. The training method is applicable for different technological systems, e.g. robot and sensor systems, or in combination with functional electrical stimulation, etc. To enable the use of TTOAT for training with the Haptic Master Robot (MOOG-FCS, NL), special software named Haptic TOAT was developed in Adelante together with colleagues at the Centre of Technology in Care of Zuyd University (chapter 6). The software enables the recording of the patient’s movement trajectories, given task constraints and patient possibilities, using the Haptic Master as a recording device. A purpose-made gimbal was attached to the endeffector, leaving the hand free for the use and manipulating objects. The recorded movement can be replayed in a passive mode or in an active mode (active, active-assisted or activeresisted). Haptic feedback is provided when the patient deviates from the recorded movement trajectory, as the patient receives the sensation of bouncing into a wall, as well as feeling a spring that pulls him/her back to the recorded path. The diameter of the tunnel around the recorded trajectory (distance to the wall), and the spring force can be adjusted for each patient. An ongoing clinical trial in which chronic stroke patients train with Haptic-TOAT examines whether Haptic Master provides additional value compared to supporting the same exercises by video-instruction only. Together with Philips Research Europe (Eindhoven,Aachen), the T-TOAT method has been implemented in a sensor based prototype, called Philips Stroke Rehabilitation Exerciser. This system included movement tracking sensors and an exercise board interacting with real life objects. A very strong feature of the system is that feedback is provided to patients (real-time and after exercise performance), based on a comparison of the patient’s exercise performance to individual targets set by the therapist. Chapter 7 reports on a clinical trial investigating arm-hand treatment outcome and patient motivation for technology-supported task-oriented training in chronic stroke patients. It was found that 8 weeks of T-TOAT training improved arm-hand performance in chronic stroke patients significantly on Fugl-Meyer, Action Research Arm Test, and Motor Activity Log. An improvement was found in health-related quality of life. Training effects lasted at least 6 months post-training. Participants reported feeling intrinsically motivated and competent to use the system. The results of this study showed that T-TOAT is feasible. Despite the small number of stroke patients tested (n=9), significant and clinically relevant improvements in skilled arm-hand performance were found. In conclusion, this thesis has made several contributions. It motivated the need for clientcentred task-oriented training, which it has operationalized in terms of 15 components. Four of these 15 components were identified as most beneficial for the patient. A prioritized inventory of arm-hand training preferences of stroke patients was compiled by means of an interview study of 40 subacute and chronic stroke patients. T-TOAT, a method for technology-supported, client-centred, task-oriented training, was conceived and implemented in two target technologies (Haptic Master and Philips Stroke Rehabilitation Exerciser). Its feasibility was demonstrated in a clinical trial showing substantial and durable benefits for the stroke patients. Finally, the thesis contributes towards the standardization of outcome measures which is necessary for charting progress and guiding future developments of technology-supported stroke rehabilitation. Methodological considerations were discussed and several suggestions for future research were presented. The variety of treatment approaches and the various ways of support and challenge that are offered by existing rehabilitation technologies hold a large potential for offering a variety of extra training opportunities to stroke patients that may improve their arm-hand performance. Such solutions will be of increasing importance, to alleviate therapists and reduce economic pressure on the health care system, as the stroke incidence is increasing rapidly over the coming decades

Stretch hyperreflexia in children with cerebral palsy:Assessment - Contextualization - Modulation

Cerebral palsy (CP) is a neurological disorder and the most frequent cause of motor impairment in children in Europe. Around 85% of children with CP experience stretch hyperreflexia, also known as “spasticity”. Stretch hyperreflexia is an excessive response to muscle stretch, leading to increased joint resistance. The joint hyper-resistance causes limitations in activities such as walking. Multiple methods have been developed to measure stretch hyperreflexia, but evidence supporting the use of these methods for diagnostics and treatment evaluation in children with CP is insufficient. Furthermore, most methods are designed to assess stretch reflexes in passive conditions, which might not translate to the limitations encountered due to stretch reflexes during activities. Furthermore, while a broad range of stretch hyperreflexia treatments is available, many are invasive, non-specific, or temporary and might have adverse side effects. Training methods to reduce stretch reflexes using biofeedback are promising non-invasive methods with potential long-term sustained effects. Still, clinical feasibility needs to be improved before implementation in clinical rehabilitation of children with CP. This thesis aimed to develop methods to assess stretch hyperreflexia of the calf muscles during passive conditions, as well as in the context of walking. Additionally, this thesis aimed to develop clinically feasible methods to modulate stretch hyperreflexia in the calf muscle of children with CP. The outcomes are described in eight different studies presented in this thesis. All in all, the work presented in this thesis shows that sagittal plane clinical gait analysis can be performed using the human body model and can be complemented with ultrasound imaging of the calf muscle. Motorized methods to assess stretch hyperreflexia in passive conditions might be useful for evaluation in adults after SCI/Stroke. Still, limitations regarding feasibility and validity limit clinical application for children with CP. Furthermore, this thesis provides additional evidence that the deviating muscle activation patterns during walking, particularly the increased activation around initial contact, are caused by stretch hyper-reflexes in children with CP. The deviating muscle activation patterns, with increased activation during early stance and reduced activation around push-off, can be modulated within one session by several children with CP. Therefore, the next step is to develop a training program to modulate the activation pattern and potentially decrease stretch hyper-reflexes in children with CP to improve the gait patter

The re-education of upper limb movement post stroke using iterative learning control mediated by electrical stimulation

An inability to perform tasks involving reaching is a common problem following stroke. Evidence supports the use of robotic therapy and electrical stimulation (ES) to reduce upper limb impairments following stroke, but current systems may not encourage maximal voluntary contribution from the participant. This study developed and tested iterative learning control (ILC) algorithms mediated by ES, using a purpose designed robotic workstation, for upper limb rehabilitation post stroke. Surface electromyography (EMG) which may be related to impaired performance and function was used to investigate seven shoulder and elbow muscle activation patterns in eight neurologically intact and five chronic stroke participants during nine tracking tasks. The participants’ forearm was supported using a hinged arm-holder, which constrained their hand to move in a two dimensional horizontal plane.Outcome measures taken prior to and after an intervention consisted of the Fugl-Meyer Assessment (FMA) and the Action Research Arm Test (ARAT), isometric force and error tracking. The intervention for stroke participants consisted of eighteen sessions in which a similar range of tracking tasks were performed with the addition of responsive electrical stimulation to their triceps muscle. A question set was developed to understand participants’ perceptions of the ILC system. Statistically significant improvements were measured (p?0.05) in: FMA motor score, unassisted tracking, and in isometric force. Statistically significant differences in muscle activation patterns were observed between stroke and neurologically intact participants for timing, amplitude and coactivation patterns. After the intervention significant changes were observed in many of these towards neurologically intact ranges. The robot–assisted therapy was well accepted and tolerated by the stroke participants. This study has demonstrated the feasibility of using ILC mediated by ES for upper limb stroke rehabilitation in the treatment of stroke patients with upper limb hemiplegia

Enhancement of Robot-Assisted Rehabilitation Outcomes of Post-Stroke Patients Using Movement-Related Cortical Potential

Post-stroke rehabilitation is essential for stroke survivors to help them regain independence and to improve their quality of life. Among various rehabilitation strategies, robot-assisted rehabilitation is an efficient method that is utilized more and more in clinical practice for motor recovery of post-stroke patients. However, excessive assistance from robotic devices during rehabilitation sessions can make patients perform motor training passively with minimal outcome. Towards the development of an efficient rehabilitation strategy, it is necessary to ensure the active participation of subjects during training sessions. This thesis uses the Electroencephalography (EEG) signal to extract the Movement-Related Cortical Potential (MRCP) pattern to be used as an indicator of the active engagement of stroke patients during rehabilitation training sessions. The MRCP pattern is also utilized in designing an adaptive rehabilitation training strategy that maximizes patients’ engagement. This project focuses on the hand motor recovery of post-stroke patients using the AMADEO rehabilitation device (Tyromotion GmbH, Austria). AMADEO is specifically developed for patients with fingers and hand motor deficits. The variations in brain activity are analyzed by extracting the MRCP pattern from the acquired EEG data during training sessions. Whereas, physical improvement in hand motor abilities is determined by two methods. One is clinical tests namely Fugl-Meyer Assessment (FMA) and Motor Assessment Scale (MAS) which include FMA-wrist, FMA-hand, MAS-hand movements, and MAS-advanced hand movements’ tests. The other method is the measurement of hand-kinematic parameters using the AMADEO assessment tool which contains hand strength measurements during flexion (force-flexion), and extension (force-extension), and Hand Range of Movement (HROM)

Development of an upper-body robotic rehabilitation platform that furthers motor recovery after neuromuscular injuries

This dissertation presents the development of an upper-body exoskeleton and its control framework for robotic rehabilitation of the arm and shoulder after a neurological disorder such as a stroke. The first step is designing an exoskeleton hardware that supports natural mobility of the human upper body with a wide range of motion for enabling most rehabilitation exercises. The exoskeleton is equipped with torque-controllable actuation units for implementing various robotic rehabilitation protocols based on force and impedance behaviors. The control framework is designed to exhibit a highly backdrivable behavior with a gravity compensation for the robot's weight and optional gravity support for user's arm weight to promote voluntary movements of patients with motor impairments. The control framework also serves as a `substrate' of other robotic control behaviors for rehabilitation exercises by superimposing desired force or impedance profiles. A stability analysis is performed to examine the coupled stability between the robot and human. After designing the hardware and control, several experiments are carried out to test the mobility and dynamic behavior of the robot. Lastly, a human subject study evaluates the effectiveness of the robot's shoulder mechanism and control algorithm in assisting the coordination around the shoulder. The results show that the robot induces desirable coordination in the presence of abnormalities at the shoulder.Mechanical Engineerin