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

Development of a hybrid robotic system based on an adaptive and associative assistance for rehabilitation of reaching movement after stroke

Stroke causes irreversible neurological damage. Depending on the location and the size of this brain injury, different body functions could result affected. One of the most common consequences is motor impairments. The level of motor impairment affectation varies between post-stroke subjects, but often, it hampers the execution of most activities of daily living. Consequently, the quality of life of the stroke population is severely decreased. The rehabilitation of the upper-limb motor functions has gained special attention in the scientific community due the poor reported prognosis of post-stroke patients for recovering normal upper-extremity function after standard rehabilitation therapy. Driven by the advance of technology and the design of new rehabilitation methods, the use of robot devices, functional electrical stimulation and brain-computer interfaces as a neuromodulation system is proposed as a novel and promising rehabilitation tools. Although the uses of these technologies present potential benefits with respect to standard rehabilitation methods, there still are some milestones to be addressed for the consolidation of these methods and techniques in clinical settings. Mentioned evidences reflect the motivation for this dissertation. This thesis presents the development and validation of a hybrid robotic system based on an adaptive and associative assistance for rehabilitation of reaching movements in post-stroke subjects. The hybrid concept refers the combined use of robotic devices with functional electrical stimulation. Adaptive feature states a tailored assistance according to the users’ motor residual capabilities, while the associative term denotes a precise pairing between the users’ motor intent and the peripheral hybrid assistance. The development of the hybrid platform comprised the following tasks: 1. The identification of the current challenges for hybrid robotic system, considering twofold perspectives: technological and clinical. The hybrid systems submitted in literature were critically reviewed for such purpose. These identified features will lead the subsequent development and method framed in this work. 2. The development and validation of a hybrid robotic system, combining a mechanical exoskeleton with functional electrical stimulation to assist the execution of functional reaching movements. Several subsystems are integrated within the hybrid platform, which interact each other to cooperatively complement the rehabilitation task. Complementary, the implementation of a controller based on functional electrical stimulation to dynamically adjust the level of assistance is addressed. The controller is conceived to tackle one of the main limitations when using electrical stimulation, i.e. the highly nonlinear and time-varying muscle response. An experimental procedure was conducted with healthy and post-stroke patients to corroborate the technical feasibility and the usability evaluation of the system. 3. The implementation of an associative strategy within the hybrid platform. Three different strategies based on electroencephalography and electromyography signals were analytically compared. The main idea is to provide a precise temporal association between the hybrid assistance delivered at the periphery (arm muscles) and the users’ own intention to move and to configure a feasible clinical setup to be use in real rehabilitation scenarios. 4. Carry out a comprehensive pilot clinical intervention considering a small cohort of patient with post-stroke patients to evaluate the different proposed concepts and assess the feasibility of using the hybrid system in rehabilitation settings. In summary, the works here presented prove the feasibility of using the hybrid robotic system as a rehabilitative tool with post-stroke subjects. Moreover, it is demonstrated the adaptive controller is able to adjust the level of assistance to achieve successful tracking movement with the affected arm. Remarkably, the accurate association in time between motor cortex activation, represented through the motor-related cortical potential measured with electroencephalography, and the supplied hybrid assistance during the execution of functional (multidegree of freedom) reaching movement facilitate distributed cortical plasticity. These results encourage the validation of the overall hybrid concept in a large clinical trial including an increased number of patients with a control group, in order to achieve more robust clinical results and confirm the presented herein.Programa Oficial de Doctorado en Ingeniería Eléctrica, Electrónica y AutomáticaPresidente: Ramón Ceres Ruiz.- Secretario: Luis Enrique Moreno Lorente.- Vocal: Antonio Olivier

Bioinspired robotic rehabilitation tool for lower limb motor learning after stroke

Mención Internacional en el título de doctorEsta tesis doctoral presenta, tras repasar la marcha humana, las principales patologíıas y condiciones que la afectan, y los distintos enfoques de rehabilitación con la correspondiente implicación neurofisiológica, el camino de investigación que desemboca en la herramienta robótica de rehabilitación y las terapias que se han desarrollado en el marco de los proyectos europeos BioMot: Smart Wearable Robots with Bioinspired Sensory-Motor Skills y HANK: European advanced exoskeleton for rehabilitation of Acquired Brain Damage (ABD) and/or spinal cord injury’s patients, y probado bajo el paraguas del proyecto europeo ASTONISH: Advancing Smart Optical Imaging and Sensing for Health y el proyecto nacional ASSOCIATE: A comprehensive and wearable robotics based approach to the rehabilitation and assistance to people with stroke and spinal cord injury.This doctoral thesis presents, after reviewing human gait, the main pathologies and conditions that affect it, and the different rehabilitation approaches with the corresponding neurophysiological implications, the research journey that leads to the development of the rehabilitation robotic tool, and the therapies that have been designed, within the framework of the European projects BioMot: Smart Wearable Robots with Bioinspired Sensory-Motor Skills and HANK: European advanced exoskeleton for rehabilitation of Acquired Brain Damage (ABD) and/or spinal cord injury’s patients and tested under the umbrella of the European project ASTONISH: Advancing Smart Optical Imaging and Sensing for Health and the national project ASSOCIATE: A comprehensive and wearable robotics based approach to the rehabilitation and assistance to people with stroke and spinal cord injury.This work has been carried out at the Neural Rehabilitation Group (NRG), Cajal Institute, Spanish National Research Council (CSIC). The research presented in this thesis has been funded by the Commission of the European Union under the BioMot project - Smart Wearable Robots with Bioinspired Sensory-Motor Skills (Grant Agreement number IFP7-ICT - 611695); under HANK Project - European advanced exoskeleton for rehabilitation of Acquired Brain Damage (ABD) and/or spinal cord injury’s patients (Grant Agreements number H2020-EU.2. - PRIORITY ’Industrial leadership’ and H2020-EU.3. - PRIORITY ’Societal challenges’ - 699796); also under the ASTONISH Project - Advancing Smart Optical Imaging and Sensing for Health (Grant Agreement number H2020-EU.2.1.1.7. - ECSEL - 692470); with financial support of Spanish Ministry of Economy and Competitiveness (MINECO) under the ASSOCIATE project - A comprehensive and wearable robotics based approach to the rehabilitation and assistance to people with stroke and spinal cord injury (Grant Agreement number 799158449-58449-45-514); and with grant RYC-2014-16613, also by Spanish Ministry of Economy and Competitiveness.Programa de Doctorado en Ingeniería Eléctrica, Electrónica y Automática por la Universidad Carlos III de MadridPresidente: Fernando Javier Brunetti Fernández.- Secretario: Dorin Sabin Copaci.- Vocal: Antonio Olivier

Down-Conditioning of Soleus Reflex Activity using Mechanical Stimuli and EMG Biofeedback

Spasticity is a common syndrome caused by various brain and neural injuries, which can severely impair walking ability and functional independence. To improve functional independence, conditioning protocols are available aimed at reducing spasticity by facilitating spinal neuroplasticity. This down-conditioning can be performed using different types of stimuli, electrical or mechanical, and reflex activity measures, EMG or impedance, used as biofeedback variable. Still, current results on effectiveness of these conditioning protocols are incomplete, making comparisons difficult. We aimed to show the within-session task- dependent and across-session long-term adaptation of a conditioning protocol based on mechanical stimuli and EMG biofeedback. However, in contrast to literature, preliminary results show that subjects were unable to successfully obtain task-dependent modulation of their soleus short-latency stretch reflex magnitude

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

The Integration of Principles of Motor Learning to Reduce Gait Asymmetry Using a Novel Robotic Device in Individuals Chronically Post-Stroke

Unilateral deficits resulting from stroke manifest as reduced velocity, decreased cadence and asymmetries in temporal, spatial and force parameters during ambulation. Gait asymmetries and compensatory strategies employed during gait result in a higher mechanical energy cost that limits activity and community participation. Despite conventional rehabilitation efforts, individuals often remain with chronic gait deficits after stroke. Robotic-based therapies have been developed as an alternative to conventional rehabilitation. These therapies offer the means to provide task-specific training at an intensity greater than that of conventional approaches; however, to date outcomes have been similar to that of conventional training. One factor potentially contributing to the limited efficacy of robotic training is the active-assist control strategy that is often employed. This type of training strategy reduces the users’ engagement in the learning process and limits skilled learning. The tethered pelvic assist device (TPAD) is a robotic device that employs actuated tethers at the pelvis to guide the user along a pre-set movement trajectory. While other robotic devices restrict movement to a fixed trajectory, the TPAD promotes shifting weight onto the paretic limb, but permits users to freely move the limb to navigate spatiotemporal aspects of training independently. This allows individuals to participate in the problem-solving process required for motor learning to occur, facilitating a more active role in the motor task itself, and thus promoting learning. Earlier work utilized the TPAD to reduce gait asymmetry in a population of individuals in the chronic phase after stroke in a single training session (Bishop et al., 2015; Vashista, 2015). Results demonstrated an increase in propulsive forces of the affected limb as a result of the intervention, but these gains did not transfer to overground gait. A follow up study explored the feasibility and efficacy of two different training strategies using the TPAD (Bishop et al., 2017). Both training strategies proved feasible and similarly efficacious. The current work examines the feasibility and preliminary efficacy of a five-day intervention using the TPAD with faded visual feedback and a short bout of task-specific overground training to reduce gait asymmetry in a population of individuals at least six months after stroke. Participants underwent a series of three Pre Test assessments within a one-week interval prior to initiating the intervention. Training occurred over five consecutive days, with a Post Test assessment administered on conclusion of Day 5 of training. A one-week Follow Up assessment was also recorded. Results demonstrated this intervention coupling TPAD training with additional tenets of motor learning including visual feedback and salient task-specific overground training was feasible in terms of safety, tolerance and adherence. Further, while participant’s load asymmetry was not significantly reduced on the treadmill from Baseline to Post Training (p >0.05), there was a significant improvement in stance symmetry during overground gait (F = 8.498, p = 0.002). These results suggest that the integration of motor learning tenets with robotic TPAD training was useful in facilitating gains to overground walking. Implications to the broader scope of robotic training suggest that creating an environment in which the user plays a more active role is useful at maximizing effects of robotic training. Future work should include comparison groups (TPAD treadmill training, overground training, and combined TPAD and overground training) with a more robust sample size for a longer duration of training to parse out contributing factors to overground gains. Future work should also consider a longer training and follow up interval in an effort to determine whether individuals are able to maintain improvements longer than the immediate post training period

Development of a Non-Invasive Brain-Computer Interface for Neurorehabilitation

Neurological disorders, in particular Stroke, have an impact on many individuals worldwide. These individuals are often left with residual motor control in their upper limbs. Although conventional therapy can aid in recovery, it is not always accessible, and the procedures are dull for the patient. Novel methods of therapy are being developed, including Brain-Computer Interfaces (BCIs). Although BCI research has been flourishing in the past few years, most rehabilitation applications are not yet suitable for clinical practice.This is due to the fact that BCI reliability and validation has not yet been achieved, and few clinical trials have been done with BCIs. Another crucial factor, is that modern BCIs are often comprised of inconvenient hardware and software. This is a major factor of aversion from both patients and clinicians. This Master Dissertation introduces the EmotivBCI: an easy to use platform for Electroencephalogram acquisition, processing and classification of sensorimotor rhythms with respect to motor action and motor imagery. The acquisition of EEG is done through 8 channels of the Emotiv Epoc wireless headset. Signals are pre-processed, and the 2 best combinations of channel/frequency pairs that exhibit the greatest spectral variation between the rest and action conditions are extracted for different time frames. These features are then used to build a feature matrix with 2 sets of attributes and 2 class labels. Finally the resulting feature matrix is used to train 3 different classifiers, in which the best is selected. The EmotivBCI enables users to keep record of their performances, and provides additional features to further examine training sessions. To assess the performance of the EmotivBCI, two studies were conducted with healthy individuals. The first study compares classification accuracies between two different training paradigms. The second study evaluates the progress in performance of a group of individuals after several training sessions